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  • Electronic Resource  (156)
  • 2000-2004  (156)
  • chemotherapy  (81)
  • Quality of life  (75)
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  • Electronic Resource  (156)
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  • 1
    ISSN: 1530-0358
    Keywords: Fecal incontinence ; Quality of life ; Health surveys ; Reproducibility of results ; Outcome assessment (health care)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: This goal of this research was to develop and evaluate the psychometrics of a health-related quality of life scale developed to address issues related specifically to fecal incontinence, the Fecal Incontinence Quality of Life Scale. METHODS: The Fecal Incontinence Quality of Life Scale is composed of a total of 29 items; these items form four scales: Lifestyle (10 items), Coping/Behavior (9 items), Depression/Self-Perception (7 items), and Embarrassment (3 items). RESULTS: Psychometric evaluation of these scales demonstrates that they are both reliable and valid. Each of the scales demonstrate stability over time (test/retest reliability) and have acceptable internal reliability (Cronbach alpha 〉0.70). Validity was assessed using discriminate and convergent techniques. Each of the four scales of the Fecal Incontinence Quality of Life Scale was capable of discriminating between patients with fecal incontinence and patients with other gastrointestinal problems. To evaluate convergent validity, the correlation of the scales in the Fecal Incontinence Quality of Life Scale with selected subscales in the SF-36 was analyzed. The scales in the Fecal Incontinence Quality of Life Scale demonstrated significant correlations with the subscales in the SF-36. CONCLUSIONS: The psychometric evaluation of the Fecal Incontinence Quality of Life Scale showed that this fecal incontinence-specific quality of life measure produces both reliable and valid measurement.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1530-0358
    Keywords: Recurrent rectal cancer ; Cost-effectiveness analysis ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: This study was performed to determine the quality of life and cost-effectiveness of therapeutic options for patients with locally recurrent rectal carcinoma, determined from the perspectives of patients and health care providers. METHODS: We reviewed the records of patients (N=68) with locally recurrent rectal carcinoma evaluated from 1992 through 1995. We constructed a decision-analytic model incorporating outcomes, survival, and costs. Utilities were elicited from convenience samples of health care providers and patients using the standard gamble technique. RESULTS: The median survival for patients undergoing surgical resection (n=40) was 42 months, compared with 16.8 months for patients undergoing diagnostic or palliative surgery (n=16) and 18.3 months for patients treated nonoperatively (n=12;P〈0.005). The mean cost of treatment per patient was $19,283 for the nonoperative group, $45,647 for the diagnostic or palliative surgery group, and $70,878 for the surgical resection group. The diagnostic or palliative surgical strategy was dominated by the nonoperative strategy because the former had greater costs with fewer health benefits. The incremental cost-utility ratio of surgical resection compared with nonoperative management using health care provider utilities was $109,777 per quality-adjusted life year gained; it was reduced to $56,698 using per quality-adjusted life year using mean patient utilities. CONCLUSIONS: Patients with recurrent rectal carcinoma view surgery and morbidity to be less severe than health care providers. Diagnostic or palliative surgery is expensive and affects quality-adjusted survival adversely compared with nonoperative therapy. Surgical resection may be a cost-effective use of resources, particularly when cost-effectiveness is calculated using patient preferences.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 326-332 
    ISSN: 1530-0358
    Keywords: Laparoscopic surgery ; Aged ; Colorectal surgery ; Morbidity ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to determine rates of complications and extent of benefits for laparoscopic-assisted colectomy compared with open colectomy in patients older than age 75. METHODS: Forty-two patients undergoing laparoscopic-assisted colectomy (1992–1998) were matched to 42 open colectomy patients for gender, age, year of surgery, operating surgeon, and procedure. Health status (American Society of Anesthesiology score), previous abdominal surgery, conversion rate, surgical outcome, and need for assistance at admission and dismissal (independencevs. home with assistancevs. nursing facilities) were reviewed. RESULTS: Mean ages were 81.2 and 80.5 years for laparoscopic-assisted colectomy and open colectomy, respectively (P=not significant). Twenty-one laparoscopic-assisted colectomy and 23 open colectomy patients were females. American Society of Anesthesiology scores were comparable, as were rates of previous abdominal surgery (57 percent for laparoscopic-assisted colectomyvs. 62 percent for open colectomy;P=not significant). Mean operative times were longer for laparoscopic-assisted colectomy (190 minutes for laparoscopic-assisted colectomyvs. 142 minutes for open colectomy;P〈0.001); operating room times progressively decreased from 221 minutes in 1992 to 1995 to 147 in 1998 for laparoscopic right hemicolectomy (P〈0.001). The conversion rate for laparoscopic-assisted colectomy was 14.3 percent. There were no deaths in either group, and laparoscopic-assisted colectomy was associated with fewer morbidities (14.3 percent for laparoscopic-assisted colectomyvs. 33.3 percent for open colectomy;P=0.04), narcotic usage (2.7vs. 4.8 days;P〈0.001), time to return to bowel movements (3.9vs. 5.9 days;P〈0.001), and length of hospital stay (6.5vs. 10.2 days;P〈0.001). Independent status at admission in 37 laparoscopic-assisted colectomy and 38 open colectomy patients was maintained at discharge by 35 laparoscopic-assisted colectomyvs. 29 open colectomy patients (P=0.025). CONCLUSIONS: Laparoscopic-assisted colectomy is safe and beneficial, including preservation of postoperative independence, to the elderly when compared with open colectomy.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Annals of surgical oncology 7 (2000), S. 367-375 
    ISSN: 1534-4681
    Keywords: Outcomes ; Surgical oncology ; Review ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: There have been significant developments and advances in the area of outcomes research in the past 25 years. Unfortunately, many surgical oncologists may not have a clear concept of outcomes research and the methodology involved. Methods: A literature-based review article was done that included an overview of outcomes research, and study design and types, outcome measures, outcome instruments, and sources of outcome data were examined. In addition, we reviewed small area variation(volume outcome analysis as well as quality-of-life studies and their applications in surgical oncology clinical investigation. Specific examples from surgical oncology were identified. Results: As the costs of health care have increased, so has the emphasis on measuring outcomes of medical and surgical care to determine the quality and appropriateness of care. Marked variations in a variety of outcomes after oncological procedures have been attributed to individual surgeon and institution characteristics. Because much of the clinical surgical oncology literature deals only with the traditional mortality and morbidity outcomes, a more comprehensive examination of patient outcomes is required to fully evaluate the impact of patient management decisions. Health-related quality of life can be measured and analyzed in several ways and decisions regarding the use of such methodology are dependent on multiple factors. Conclusions: Surgical oncologists should recognize that the true value of their interventions requires systematic and comprehensive examination of patient outcomes.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1534-4681
    Keywords: Breast cancer ; Quality of life ; Mental health ; Surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The aim of the present study was to examine whether type of surgery, age, and time since surgery influenced psychological distress and quality of life (QOL) in women treated for breast cancer. Methods: We surveyed 183 women who had undergone surgery for breast cancer. Psychological distress was measured with the Mental Health Inventory and QOL was measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Results: After controlling for stage of disease, radiation treatment, and age, there was a statistically significant interaction between type of surgery and time since surgery for the Mental Health Inventory total score, and a marginal interaction between type of surgery and time since surgery for the Global health status/QOL score. Women who had breast conservation surgery experienced significantly greater levels of psychological distress and marginally worse QOL from 40 months after surgery onward than did women who received a mastectomy. Conclusions: The effects of different surgical treatments for breast cancer on psychological distress and QOL become apparent only after a period of several years. Women, therefore, need counseling on the potentially positive and negative psychological implications of different surgical treatments for breast cancer.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 1497-1502 
    ISSN: 1530-0358
    Keywords: Ulcerative colitis ; Quality of life ; Pelvic pouch ; Dysplasia ; Cancer ; Colitis-associated neoplasia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Despite high patient satisfaction with a pelvic pouch, patients experience some bowel dysfunction. Patients whose indication for surgery is neoplasia may have near-normal preoperative bowel function. We hypothesized that these patients would be less accepting of a poorer functional status after surgery, reflected in a poorer measure of quality of life. METHOD: Sixteen patients who had dysplasia or cancer as the primary indication for surgery were compared with a matched control group whose indication for surgery was failed medical therapy. Quality of life was assessed using one disease-specific instrument, the Inflammatory Bowel Disease Questionnaire, two generic quality-of-life instruments, the Sickness Impact Profile and the Short Form 36, and two utility assessments. RESULTS: The groups were well matched with no significant differences in functional outcome. Quality-of-life scores were high in both groups and there were no significant differences in overall quality of life between the two groups using all five instruments. There was evidence of a response shift phenomenon in the failed medical therapy control group. CONCLUSION: Quality of life of patients who have a pelvic pouch for colitis-associated neoplasia is excellent and the same as that of patients who have a pouch for failure of medical therapy.
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  • 7
    ISSN: 1530-0358
    Keywords: Rectal cancer ; Sphincter preservation ; Functional outcome ; Quality of life ; Intraoperative radiation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Locally advanced primary and recurrent rectal cancers treated with external beam radiation therapy, intraoperative radiation therapy, and chemotherapy represent a complex group of patients in the setting of extensive pelvic surgery and sphincter preservation. We sought to define functional outcome and quality of life in this subset of patients. METHODS: We retrospectively reviewed our experience with locally advanced primary and recurrent rectal cancer patients who underwent intraoperative radiation therapy with either low anterior resection (n=12) or coloanal anastomosis (n=6) between 1991 and 1998. Current functional outcome and quality of life were evaluated by a detailed questionnaire. RESULTS: Median time from operation to assessment was 24 (range, 6–93) months. Using a standardized Sphincter Function Scale, incorporating the number of bowel movements per day and degree of incontinence, patients were graded as poor, fair, good, or excellent function. Of all patients, 56 percent reported unfavorable (poor or fair) function. Of the subset of patients with coloanal anastomosis or very low low anterior resection, 88 percent had unfavorable function as compared with 30 percent with standard low anterior resection. (P=0.02; Fisher's exact probability test). A quality-of-life satisfaction score based on social, professional, and recreational restrictions demonstrated 56 percent of patients to be dissatisfied with their bowel function. CONCLUSIONS: The majority of patients with advanced rectal cancers who require external beam radiation therapy, extensive pelvic surgery, and intraoperative radiation therapy report unfavorable functional and quality-of-life outcomes after sphincter preservation. In this setting patients being considered for coloanal anastomosis or very low anterior resection may be better served by permanent diversion.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 1206-1212 
    ISSN: 1530-0358
    Keywords: Fistula-in-ano ; Recurrence ; Incontinence ; Quality of life ; Lifestyle ; Satisfaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The surgical treatment of fistula-in-ano frequently results in recurrence of the fistula or postoperative anal incontinence. Despite these problems, most patients are satisfied with the results of their surgery. To clarify this apparent discrepancy, we attempted to identify factors that affect patient's lifestyles and may contribute to their satisfaction. METHODS: A questionnaire was mailed to 624 patients surgically treated for cryptoglandular fistula-in-ano at the University of Minnesota during a five-year period. Three hundred seventy-five patients returned their questionnaires. Patients who were followed up for a minimum of one year were included in this retrospective study. Associations between postoperative complications and patient satisfaction were identified by chi-squared tests and multiple logistic regression. Attributable fractions for patient dissatisfaction were calculated using study population dissatisfaction rates. RESULTS: Patient satisfaction was strongly associated with fistula recurrence, difficulty holding gas, soiling of undergarment, and accidental bowel movements. Effects of incontinence on patient quality of life were also significantly associated with patient satisfaction as was the number of lifestyle activities affected by incontinence. Patients with fistula recurrence reported a higher dissatisfaction rate (61 percent) than did patients with anal incontinence (24 percent), but the attributable fraction of dissatisfaction for incontinence (84 percent) was greater than that for fistula recurrence (33 percent). Patient satisfaction was not significantly associated with age, gender, history of previous fistula surgery, type of fistula, surgical procedure, time since surgery, or operating surgeon. CONCLUSION: Patient satisfaction after surgical treatment for fistula-in-ano is associated with recurrence of the fistula, the development of anal incontinence, and with the effects of anal incontinence on patient lifestyle. In our series of patients treated mainly with laying open of the fistula tract, patients with fistula recurrence had a higher dissatisfaction rate than did patients with anal incontinence. However, because anal incontinence was more prevalent than fistula recurrence, a higher fraction of dissatisfaction was attributable to anal incontinence.
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  • 9
    ISSN: 1534-4681
    Keywords: Quality of life ; Cystectomy ; Urinary diversion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In this study, we used a previously well-validated survey to assess the impact of different forms of urinary diversion on overall quality of life in patients with bladder cancer. Methods: A total of 92 patients, having three different forms of urinary diversion after radical cystectomy, completed by mail the SF-36, a validated quality-of-life survey. All patients had local(regional disease at the time of cystectomy and are currently without evidence of disease. Completed surveys were then analyzed into physical (PCS) and mental (MCS) component quality-of-life scores per published protocols. Results were then compared with published age-based norms. Results: A total of 38 men who had cystectomy and ileal neobladder had a mean PCS (6SD) of 48.4 (7.8) and a mean MCS of 51.0 (7.4); 16 men and women who had cystectomy and Indiana Pouch had a mean PCS of 48.4 (8.9) and a mean MCS of 55.7 (3.8). None of these results is statistically different from published age- and sex-based population norms. Thirty-eight men who had cystectomy and ileal conduit had a mean PCS of 41.4 (8.5) and a mean MCS of 48.2 (10.7). The PCS is not statistically different from the population-based norm; however, the MCS is significantly decreased from the published norm (P 5.01). Conclusions: Patients with ileal conduits have significantly decreased mental health quality of life whereas patients with continent urinary diversions do not. Therefore, when not medically contraindicated, patients should be offered a continent diversion as the diversion of choice after cystectomy.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 650-655 
    ISSN: 1530-0358
    Keywords: Loop ileostomy ; Loop colostomy ; Quality of life ; Stoma complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The hypothesis is that the impact of a temporary stoma on a patient's daily life is determined by complications and related stoma care problems. METHOD: A prospective clinical trial was performed, studying complications and social well-being of 37 patients with loop ileostomy and 39 patients with a loop colostomy (randomly assigned comparison). Patients were categorized according to degree of social restriction. The association between the degree of social restriction and the presence of stoma care problems and complications was assessed. Follow-up was scheduled every three months until the stoma was closed (94 percent). RESULTS: There is no relation between stoma type (ileostomy or colostomy) and degree of social restriction (chi-squared test,P=0.42). The more stoma care problems or complications seen, the higher the degree of social restriction: significantly more stoma care problems were seen in the completely isolated group of patients when compared with the patients who were less socially restricted (Spearman correlation coefficient 1=0.35,P=0.003). Especially stoma leakage, peristomal skin irritation, dietary prescriptions, retraction, and prolapse of the stoma have significant impact on the patient's daily life. CONCLUSION: Stoma surgery has a great influence on a patient's daily life. There is a clear relation between the number of stoma care problems and the degree of social restriction. Follow-up of stoma patients under close surveillance of stoma care nurse to minimize stoma care problems and a careful surgical technique are advocated for good stoma care.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Journal of gastroenterology 35 (2000), S. 907-911 
    ISSN: 1435-5922
    Keywords: Key words: gastric cancer ; liver neoplasms ; secondary ; interventional radiology ; chemotherapy ; chemoembolization ; therapeutic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Little is known about the effectiveness of transcatheter chemotherapy in liver metastases from gastric cancer. The aim of this study was to evaluate the initial results of hepatic artery infusion and oily chemoembolization in these liver secondaries. Courses of transcatheter arterial infusion with 5-fluorouracil/doxorubicin (12 patients) and oily chemoembolization with doxorubicin-in-iodized oil and gelatin sponge (12 patients) were performed in 24 patients with histologically proven unresectable gastric cancer liver metastases. A positive effect of treatment (partial response + stabilization) was seen in 92% of the patients after chemoinfusion and in 50% after chemoembolization. The 1- and 2-year actuarial survival rates were 92% and 53% for infusion vs 50% and 17% for chemoembolization, respectively (log-rank test, P = 0.0009). For patients who had already died, the mean survival was 19.2 months vs 9.5 months (Student's t-test, P 〈 0.05) with median survivals of 23 months vs 8 months, respectively. The results with arterial infusion were very close to those reported for liver resection. Transcatheter therapy appears to be useful for the palliation of unresectable liver metastases from gastric cancer. If regional chemotherapy is used, arterial infusion should be the first-choice treatment, with oily chemoembolization being reserved for patients who do not respond to infusion.
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  • 12
    ISSN: 1569-8041
    Keywords: chemotherapy ; docetaxel ; gastric cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:A multi-centric trial was performed to explore theclinical activity, in terms of response and toxicity (primary objectives),duration of response and survival (secondary objectives), of docetaxel withcisplatin in advanced gastric cancer (AGC). Patients and methods:Patients with measurable unresectable and/ormetastatic gastric carcinoma, performance status ≤1, normal hematological,hepatic and renal functions and not pretreated for advanced disease bychemotherapy received up to eight cycles of TC (docetaxel 85 mg/m2d1, cisplatin 75 mg/m2 d1) q3w. Dose escalation to 100mg/m2 was performed in five patients and was discontinued forexcessive toxicity. Results:Forty-eight patients were accrued. A median of 5cycles/patient was given. We observed 2 complete and 25 partial responses foran overall intent to treat response rate of 56% (95% CI:41%–71%). Twelve patients had stable disease for ≥9weeks (3 cycles). The median time to progression and overall survival were 6.6and 9 months, respectively. Grade ≥3 toxicities were neutropenia81%, anemia 32%, thrombocytopenia 4%, alopecia36%, fatigue 9%, mucositis 9%, diarrhea 6%,nausea/vomiting 4%, neurologic 2%, and one anaphylaxisprecluding treatment administration. We recorded nine episodes of non-fatalfebrile neutropenia in eight patients, two of them with docetaxel at 100mg/m2. There were no direct treatment-related deaths. Conclusions:TC is active in AGC with a high response rate in amulticentric trial. Despite its hematotoxicity, this regimen is well toleratedand can be recycled as originally planned in 78% of the cases. Theseresults may serve as basis for further developments of docetaxel containingregimens in this disease.
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  • 13
    ISSN: 1569-8041
    Keywords: chemotherapy ; concomitant chemoradiotherapy ; head and neck cancer ; paclitaxel ; radiation ; reirradiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Concomitant chemoradiotherapy is an effectivetreatment modality for advanced head and neck cancer, but improved regimensare needed. We sought to define the toxicities, recommended phase II dose, andoutcome of a combination chemotherapy regimen with concomitanthyperfractionated radiotherapy in patients with poor prognosis cancers of thehead and neck, including those having received prior curative intentradiotherapy. Patients and methods:From 1995 until 1997, 54 patients weretreated, 25 of whom had received a prior full course of radiotherapy to thehead and neck. Patients were treated with 5-fluorouracil (5-FU) 600mg/m2/day continuous infusion × 5 days (days 1–5),hydroxyurea, 500 mg p.o. bid × 11 doses (days 1–6) and paclitaxel(60–150 mg/m2) by one-hour infusion on day 2 using a doseescalation strategy. Radiotherapy was given concomitantly on days 2–6,150 cGy bid. Each of 4–5 cycles was delivered every other week. Results:The MTD of paclitaxel was 100 mg/m2. Theregimen was feasible; radiotherapy was delivered at a median of 7300 cGy and83% of patients received ≥80% planned dose intensity.Hematological toxicity, with granulocyte colony stimulating factor, was verymild. Dose limiting toxicities were mucositis and dermatitis. Despite poorprognosis, two-year survival was 45%. Conclusions:The recommended phase II dose of this regimen is 5-FU600 mg/m2/day × 120 hours (days 1–5), hydroxyurea 500mg p.o. b.i.d. × 11 doses (days 1–6), paclitaxel 100mg/m2 over one hour on day 2, and radiotherapy 150 cGy b.i.d. days2–6. Concomitant chemotherapy and re-irradiation was feasible on thisprotocol and resulted in long-term survival in patients without other curativeintent options.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 11 (2000), S. 887-889 
    ISSN: 1569-8041
    Keywords: chemotherapy ; lung metastases ; spontaneous pneumothorax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Pneumothorax occurring in the absence of obvious lungdisease is defined as spontaneous pneumothorax. Spontaneous pneumothoraxoccurs in a variety of settings in patients with malignancies. Patients and methods:We present a case report of spontaneouspneumothorax in malignancy and review the literature. Results:No correlation was found between the occurrence ofpneumothorax with age, sex or smoking history. Pneumothorax occurred with avariety of primary tumors. However it was always associated with lungmetastases or lung involvement with tumor. In certain cases the metastaseswere detected after the occurrence of pneumothorax. Conclusions:The occurrence of pneumothorax in a patient withmalignancy should prompt a search for lung metastases.
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  • 15
    ISSN: 1569-8041
    Keywords: carboplatin ; chemotherapy ; gemcitabine ; non-small-cell lung cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The combination of paclitaxel (P) and carboplatin (C)is an effective treatment for advanced NSCLC. Gemcitabine (G) is an active newdrug. We planned a phase I study to find the maximum tolerated dose (MTD) ofthe PCG combination. A phase II study was subsequently conducted to evaluatethe activity and toxicity of PCG. Patients and methods:Forty-five patients entered the study.Twenty-eight had stage IIIA–B disease, 17 stage IV. In the phase Istudy, with a fixed dose of C at AUC = 6 on day 1, P was escalated usingincrements of 25 mg/m2 starting from 175 mg/m2 on day1 and G with increments of 200 mg/m2 starting from 800mg/m2 on day 1 and 8. Results:Fourteen patients entered the phase I study. The MTD wasreached at P 200 mg/m2, C AUC = 6 and G 1000 mg/m2.Neutropenic fever and grade 3 diarrhea were the dose limiting toxicities.Thirty-one patients were treated in the phase II study with P 175mg/m2, C AUC = 6 and G 1000 mg/m2. Response rate was57% (68% in stage III and 47% in stage IV).Myelosuppression was the main toxicity, with grade 3–4 leukopeniaoccurring in 35% of cases. Grade 3 anemia was observed in 24%of cases and grade 3–4 thrombocytopenia occurred in 34% ofpatients. Non-hematological toxicity was mild. Median survival and one-yearactuarial survival were 20.5 months and 74% for stage III and 11.5months and 47% for stage IV. Conclusions:PCG is a promising regimen for treating advancedNSCLC. A phase III study comparing PCG to paclitaxel plus carboplatin inadvanced NSCLC is ongoing. On the other hand, we are planning to introduce thePCG regimen in the treatment of stage II–III patients in the setting ofa multimodality treatment.
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  • 16
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; malignant glioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:We conducted a phase II multicentre study of gemcitabinein patients with anaplastic astrocytoma and glioblastoma multiforme at firstrelapse. Patients and methods:Patients with anaplastic astrocytoma orglioblastoma multiforme receiving a stable dose of steroids and ECOGperformance status ≤3 were eligible for this study at the time of firstrelapse. One adjuvant chemotherapy regimen was permissible. Patients receivedgemcitabine 1000 mg/m2 i.v. weekly × 3, repeated on afour-weekly cycle. Results:Of 20 patients enrolled, 15 were evaluable for response,19 for non-hematological toxicity and 18 for hematological toxicity. Sevenpatients had anaplastic astrocytoma (AA) and twelve glioblastoma multiforme(GBM). Age ranged from 28–71 years (median 50). Fifteen patientsdiscontinued therapy due to disease progression. The median number of cyclesadministered was 1 (range 1–11); only two patients received more thanthree cycles. Hematologic toxicity was acceptable and no grade 4 toxicity wasseen. One patient developed Pneumocystispneumonia and eventualpulmonary embolism; one died of gastric hemorrhage related to steroid therapy.No objective responses were seen. Nine patients had stable disease (medianduration 2.7 months, range 0.9–11.2). Conclusions:Gemcitabine given in this dose and schedule seemswell tolerated but is not active in patients with recurrent high-gradegliomas.
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  • 17
    ISSN: 1569-8041
    Keywords: alkylating agents ; bendamustine ; chemotherapy ; phase I study ; solid tumours ; weekly chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The cytotoxic agent bendamustine combines apurine-like benzimidazol and alkylating nitrogen mustard group. The clinicallytolerated dose for single bolus bendamustine is 215 mg/m2, forfractionated therapy on four consecutive days 85 mg/m2. The maximumtolerated dose of a day 1 and 8 (q4w) 30 min infusion schedule was recentlyfound to be 160 mg/m2, mouth dryness and fatigue weredose-limiting. Our current phase I trial was designed to define therecommended dose of a new weekly short infusion schedule. Patients and methods:Patients with refractory malignant tumoursqualified for the trial after written informed consent was obtained.Bendamustine was given as a 30-min i.v. infusion weekly for up to eightconsecutive weeks. Results:Twelve patients (8 male, 4 female, median age 57.5 years,range 42–64) were enrolled in this trial. At the starting dose of 80mg/m2, two patients had dose-limiting toxicity (fatigue grade 3,mouth dryness grade 3, fever grade 4 Common Toxicity Criteria). Nodose-limiting events were observed in six patients treated at 60mg/m2. An intermediate dose level of 70 mg/m2 wasstudied in three younger, less heavily pre-treated patients, was welltolerated and not associated with dose-limiting events. Haematologicaltoxicity was mild except for grade 3–4 lymphocytopenia, occurring in 11of 12 patients. Bendamustine was found to induce long-lastingpanlymphocytopenia with predominant B-cell cytotoxicity. Conclusions:The maximum tolerated dose of weekly bendamustinegiven as a 30-min i.v. infusion is 80 mg/m2, mouth dryness, fatigueand fever are dose-limiting. The recommended dose for phase II trials is 60mg/m2.
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  • 18
    ISSN: 1569-8041
    Keywords: anthracycline ; chemotherapy ; liposomal daunorubicin ; lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Standard therapy for lymphoma consists of acyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P) (CHOP)combination regimen. Liposomal daunorubicin (DaunoXome®) is an alternativeto doxorubicin for patients with lymphoma because of its more favorable safetyprofile and potentially more selective uptake in lymphoma. The objectives ofthis study were to determine the maximum tolerated dose (MTD) of liposomaldaunorubucin with CVP (COP-X) and the tolerability of the regimen in patientswith indolent lymphoma. Patients and methods:Patients with low-grade andintermediate-grade lymphoma having adequate cardiac, hepatic, and renalfunction were enrolled. Patients received C 750 mg/m2, V 1.4mg/m2 (maximum 2.0 mg), and liposomal daunorubicin 50–100mg/m2 i.v. on day 1 and P 100 mg p.o. on days 1–5. MTD wasthe liposomal daunorubicin dose associated with 20% dose-limitingtoxicity (ANC 〈500/mm3 for 〉5 days or febrile neutropenia). Results:Twenty patients, median age 59 years, were treated. Theliposomal daunorubicin MTD combined with CVP was 70–80 mg/m2,depending on patient population. No significant non-hematologic toxicityoccurred. Response rate was 44% (2 complete and 5 partial responses). Conclusions:A liposomal daunorubicin dose of 80 mg/m2in the COP-X regimen was well tolerated with little non-hematologic toxicity.
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  • 19
    ISSN: 1569-8041
    Keywords: adjuvant ; chemotherapy ; gastric cancer ; meta-analysis ; randomised clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Several studies have investigated the possible roleof the adjuvant chemotherapy after curative resection for gastric cancerfailing to show a clear indication; previous meta-analyses suggested smallsurvival benefit of adjuvant chemotherapy, but the statistical methods usedwere open to criticisms. Materials and methods:Randomised trials were identified by meansof Medline and CancerLit and by selecting references from relevant articles.Systematic review of all randomised clinical trials of adjuvant chemotherapyfor gastric cancer compared with surgery alone, published before January 2000,were considered. Pooling of data was performed using the fixed effect model.Death for any cause was the study endpoint. The hazard ratio and its95% confidence intervals (95% CI), derived according to themethod of Parmar, were the statistics chosen for summarising the relativebenefit of chemotherapyversuscontrol. Results:Overall 20 articles (21 comparisons) were considered foranalysis. Three studies used single agent chemotherapy, seven combination of5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU withoutanthracyclines. Information on 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82,95% CI: 0.75–0.89, P 〈 0.001). Association ofAnthracyclines to 5-FU did not show a statistically significant improvementwhen compared with the effect of the other regimens. Conclusions:Chemotherapy produces a small survival benefit inpatients with curatively resected gastric cancer. However, taking into accountthe limitations of literature based meta-analyses, adjuvant chemotherapy isstill to be considered as an investigational approach.
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  • 20
    ISSN: 1569-8041
    Keywords: chemotherapy ; chromosome aberrations ; malignant germ-cell tumours
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Ethik in der Medizin 12 (2000), S. 139-153 
    ISSN: 1437-1618
    Keywords: Key words: Motion pictures ; Medical ethics ; Physician-patient relationship ; Truth disclosure ; Informed consent ; Third-party consent ; Quality of life ; Euthanasia ; Terminally ill ; Schlüsselwörter: Film ; Medizinethik ; Arzt-Patient Beziehung ; Aufklärung ; Wahrheit sagen ; informed consent ; Lebensqualität ; Sterbehilfe ; Heilversuche
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Philosophy
    Description / Table of Contents: Zusammenfassung. Filme erzählen Geschichten. Spannungsvoll sind dabei vor allem jene Szenen, in denen Menschen vor Entscheidungskonflikte gestellt werden. Medizinethische Konflikte tauchen dabei nicht nur in Arztserien oder Krankheitsdarstellungen auf, sondern häufig in Genres, in denen diese Thematik kaum vermutet wird: Komödien, Western, Liebesfilmen, Gangster- und Kriminalfilmen. Indem Filme derartige Konflikte inszenieren und Lösungen bieten, greifen sie auf moralische Werthaltungen zurück und sind zugleich Seismographen für die gesellschaftliche Relevanz medizinethischer Themenfelder. Allerdings können im Film ethische Prinzipien der Entscheidungsfindung der Dramaturgie der Handlung zum Opfer fallen. Eine Analyse der dargestellten Konfliktsituationen ähnelt einer medizinethischen Fallbesprechung und stellt eine hilfreiche Ergänzung für die Vermittlung analytischer und kommunikativer Kompetenzen dar.
    Notes: Abstract. Movies tell stories. Thrilling are especially those situations, when people have to make ethical decisions. Issues of medical ethics crop up not only in hospital series, but often in genres where this subject is hardly to be supposed: comedies, westerns, love stories and gangster movies. Enacting these conflicts means offering a solution, and in doing so films refer to moral values and – at the same time – function as seismographs for the social relevance of bioethical topics. But it is possible that ethical principles of good decision-making fall victims to the drama of the story. Analysis of the portrayed conflict is similar to a case discussion in bioethics and represents a helpful adjunct to the procurement of analytical and communicative competences.
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  • 22
    ISSN: 1569-8041
    Keywords: chemotherapy ; drug interaction ; in vitroassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Chemotherapy using multi-drug regimens is consideredmore active than single-agent therapy. This may be due to synergisticinteractions or, simply, a higher probability of administering an activeagent. We investigated in vitrothe type of drug interactions in arecognized regimen in relationship to tumour type and drug sensitivity. Patients and methods: The possibility of synergistic and additiveinteractions between individual cytotoxic drugs was investigated for thecomponent drugs of the established FEC regimen, i.e., 5-fluorouracil,epirubicin and cyclophosphamide, in 243 patient tumour samples representingvarious drug sensitivity using the non-clonogenic fluorometric microculturecytotoxicity assay. Results: Using a cell survival of ≤50% as a limit fordrug activity and sample sensitivity, the overall response rates to the mostactive single drug (Dmax) and the combination were 56% and64%, respectively, with a distribution among diagnoses similar to thatin the clinic. For 86% of the samples there was concordance withrespect to judgement of activity using either Dmax or thecombination. For samples being sensitive to at least one single drug,95% were also sensitive to the combination whereas for samples withinsignificant Dmax effect, only 2% were sensitive to thecombination. In samples with modest Dmax effects, i.e., cellsurvival in the range 〉50%–≤80%, 45%responded to the combination. The effect of the combination was generally wellpredicted from the Dmax effect. Conclusions:The superior antitumour effect of drug combinationscompared with single drugs may be due to the higher chance of selecting anactive agent. However, for intermediately sensitive tumours, additionalinteraction effects of a combination may be of clinical significance.
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  • 23
    ISSN: 1569-8041
    Keywords: chemotherapy ; ovarian cancer ; second-line
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine is active in patients with otherwiseresistant or refractory ovarian cancer. As the drug is well tolerated, studiesusing gemcitabine combined with other antineoplastic agents are needed. Theaim of the study was to determine the maximum tolerated dose (MTD) ofepirubicin combined with gemcitabine, with and without support of G-CSF. Patients and methods:Patients with platinum-resistant orrefractory ovarian cancer were eligible. Gemcitabine (G) (starting dose 800mg/m2 day 1 and 8; 200 mg/m2 escalation per level) andepirubicin (E) (starting dose 60 mg/m2 day 1; 15 mg/m2escalation per level) were given every 21 days for four to six cycles. G-CSF(filgrastim 5 µg/kg/die) was given in case of grade 4 neutropenia(levels without support) or from day 9 up to leukocyte count〉10,000/mm3 after nadir (levels with support). Cohorts of threepatients were enrolled at each level, and another three patients were planned,if one dose-limiting toxicity (DLT) was registered. MTD was determined firstwithout and then with G-CSF. Results:Four levels were studied (G 800 + E 60; G 1000 + E 60;G 1000 + E 75; G 1000 + E 75 + G-CSF) with four, four, three and threepatients enrolled, respectively. DLT (grade 4 febrile neutropenia) wasobserved in two patients at level 3. Thus, G1000 + E 60 mg/m2 wasthe MTD without G-CSF. The addition of prophylactic G-CSF did not allow afurther increase of the dose and grade 4 thrombocytopenia was the DLT at level4. Non-hematological toxicity was mild. Grade 2 mucositis was reported in fourpatients. Among the 13 patients with measurable or evaluable disease, 3partial responses were observed for an overall response rate of 23.1%. Conclusions:The combination of gemcitabine 1000 mg/m2(day 1, 8) and epirubicin at 60 mg/m2 (day 1) is a feasibletherapy. Grade 4 neutropenia is frequent and G-CSF support is often required.With prophylactic support of G-CSF, the DLT is thrombocytopenia.
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  • 24
    ISSN: 1569-8041
    Keywords: brain tumor ; chemotherapy ; encephalopathy ; late neurological toxicity ; leucoencephalopathy ; primary cerebral lymphoma ; radiochemotherapy ; systematic follow-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Primary cerebral non-Hodgkin's lymphomas (NHL) inimmunocompetent patients (PCL) are located exclusively in the central nervoussystem, the eye, or meninges. Clinical management of these patients remainscontroversial. Patients and methods:Clinical characteristics of the patients andparameters influencing their outcome as of December 1998 were investigated andregistered in a database of 226 patients treated in the French Federation ofCancer Centers between 1980 and 1995. Results:Most PCL are diffuse large-cell NHL with a B phenotype.The incidence of PCL has been steadily increasing over the past 20 years insome but not all countries. The overall survival of primary cerebral lymphoma(PCL) patients in the published series, a median of 12–16 months and afive-year survival of 5%–20%, is poor. Several series havenow reported long-term survivals of more than 10 years and PCL may thereforebe a curable tumor in some patients. The optimal treatment of PCL is notknown. Complete resection of the tumor does not improve outcome andmultidisciplinary approaches combining chemotherapy and radiotherapy are nowcommonly used, although the superiority of combination over radiotherapy- orchemotherapy-alone has never been demonstrated in a phase III trial. Theoptimal chemotherapy regimen, the dose and even the usefulness of brainradiotherapy after chemotherapy are therefore still matters of debate.Recently, several authors have reported a relatively high incidence of lateneurological sequelae after PCL treatment. Conclusions:The optimal treatment of PCL patients remains to bedefined. Large cooperative international phase III trials are now required todefine and improve the optimal treatment of PCL and reduce its sequelae.
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  • 25
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    Annals of oncology 11 (2000), S. 81-85 
    ISSN: 1569-8041
    Keywords: ABVD ; BEACOPP ; chemotherapy ; clinical trials ; COPP ; dose intensification ; Hodgkin's disease ; radiotherapy ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Treatment strategies in Hodgkin's disease (HD) arechanging fundamentally over the last decades. Both radiotherapy andcombination chemotherapy are effective treatment modalities. However, theoptimal choice of treatment or combinations of treatment is still debated fordifferent prognostic groups. Patients and methods:The German Hodgkin's Lymphoma Study Group(GHSG) initiated randomized clinical trials since 1978. Over the past 20years, more than 6000 patients with HD in all stages were randomized, treatedand followed by the GHSG. Patients are now being recruited from more than 300clinical centers. Results:As a consequence of different clinical trials, it is nowthe policy of the GHSG to tailor treatment to the individual risk of patients,giving favorable patients less intensive and less toxic therapy thanunfavorable patients. The treatment for early and intermediate stage HDbecomes quite similar with few cycles of polychemotherapy followed by involvedfield irradiation. In advanced stage HD, the introduction of dose intensifiedchemotherapy (BEACOPP), has improved treatment results and thus willsubstitute the MOPP or ABVD regimens. Conclusions:Although most of the patients with HD will be curedby modern treatment stategies, several questions are still subjects of ongoingclinical trials: 1) which chemotherapy regimen in which quantity will be thebest with respect to efficacy and toxicity and 2) which dose and field sizeof radiotherapy is adequate within the combined modality.
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  • 26
    ISSN: 1569-8041
    Keywords: antifolate ; chemotherapy ; pancreatic cancer ; thymidylate synthase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:To determine the safety and activity of LY231514(ALIMTA™, MTA, pemetrexed disodium, Eli Lilly and Co.,Indianapolis, IN) in chemotherapy-naïve patients with advanced pancreaticcancer. Patients and methods:Patients with unresectable or metastaticpancreatic cancer received LY231514 600 mg/m2 as a 10–minuteinfusion every three weeks. Results:Forty-two patients were enrolled in this phase II trial.The median age was 60.3 (range 37–77) years; 79% had metastaticdisease. Neutropenia was common (40% of patients ≥ grade 3) butinfectious complications were rare. Significant anemia or thrombocytopeniaoccurred in 〈20% of patients. Non-hematologic toxicities includedgrade 2 or 3 skin reaction which was ameliorated by dexamethasone. Elevationsof bilirubin or transaminases were infrequent (〈25% of patients) anddid not require dose reductions or treatment delays. Thirty-five patientsreceived two cycles of therapy and were evaluable for response. One complete(duration 16.2 months) and one partial (duration 6.9 months) were observedresulting in an objective response rate of 5.7% for evaluable patients.In addition, 17 patients (40%) had stable disease that lasted ≥6months in 5 patients. The median survival was 6.5 months, with 28% ofpatients alive at one year. Conclusions:LY231514 is a well-tolerated agent with minimalobjective antitumor activity in pancreatic cancer. The median and one yearsurvival times, which may be important indicators in phase II trials of newagents, are of interest. Combination trials of LY231514 in pancreatic cancerare planned.
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  • 27
    ISSN: 1569-8041
    Keywords: chemotherapy ; 5-FU ; folinic acid ; gemcitabine ; Gemzar® ; pancreas cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine (Gemzar®) and 5-fluorouracil (5-FU)plus folinic acid (FA) both have proven activity in the treatment of patientswith advanced pancreatic cancer. The present study was initiated toinvestigate the efficacy of gemcitabine in combination with 5-FU–FA. Patients and methods:Thirty-eight patients, median age 60 years(range 34–70) with inoperable, stage IV, pancreatic cancer were enrolledinto the study and treated on an outpatient basis. All except one patientreceived at least one cycle of treatment with gemcitabine (1000mg/m2), followed by FA (200 mg/m2) and 5-FU (750mg/m2) administered as a 24-hour continuous infusion on days 1, 8,15 and 22 of a 42-day schedule. No patient had received prior chemotherapy orradiotherapy. All 38 patients were assessed for efficacy, toxicity and timeto progressive disease. Results:Two patients (5%), achieved a partial response andthirty-four patients (89%) achieved stable disease. There were twoearly deaths (≤4 weeks). The median time to progression was 7.1 months(range 0.4–18.1+; 95% confidence interval (95% CI):5.3–7.9 months). Three patients had a progression-free interval ofgreater than 12 months and 12 of 38 patients (32%) survived longer than12 months. The median overall survival was 9.3 months (range 0.5–26.5;95% CI: 7.3–13.0 months). The incidence of grade 3 and 4toxicities was low. Conclusions:The combination of gemcitabine and 5-FU–FA isactive and well tolerated and seems to offer an improvement inprogression-free interval over both gemcitabine monotherapy and 5-FU–FAtherapy.
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  • 28
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; arterial access device ; chemotherapy ; colorectal cancer ; hepatic arterial chemotherapy ; liver metastases ; port-a-cath
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Hepatic arterial chemotherapy for liver metastases ofcolorectal cancer is still under discussion. Mainly because of the technicalcomplications of this mode of treatment and the lack of a survival benefit inrandomized studies. We performed an analysis of hepatic arterial5-fluorouracil (5-FU) chemotherapy in 145 consecutive patients treated at asingle institution. Patients and methods:One hundred forty-five patients withinoperable liver metastases from colorectal cancer were included. 5-FU, 1000mg/m2/day continuous infusion for five days every three weeks, wasdelivered in the hepatic artery by percutaneous catheter or arterial accessdevice. Results:The response rate was 34% for all patients,40% in patients with extrahepatic disease, and 15% in patientswith i.v. 5-FU-based pretreatment. TTP and OS for all patients were 7.5 and14.3 months, respectively. In patients with extrahepatic disease or i.v.5-FU-based pretreatment, OS was significantly shorter compared to patientswithout extrahepatic disease or 5-FU-based pretreatment (9.7 vs. 19.3 monthsand 10.1 vs. 17.4 months, respectively). forty-seven percent of patientsstopped treatment because of a complication. Complications most often seen inpatients with arterial ports were hepatic artery thrombosis (48%) anddislocation of the catheter (22%). Conclusions:The results of our analysis are in line with previousphase III studies. Extrahepatic disease and i.v. 5-FU-based pretreatment wereprognostic for reduced OS. The complication rate of hepatic arterial deliverywas worrisome, although, no negative impact on survival could be established.There is a strong need for improvement of hepatic arterial delivery methodsbefore further evaluation of hepatic arterial 5-FU will be worthwhile.
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  • 29
    ISSN: 1569-8041
    Keywords: autologous stem-cell transplantation ; chemotherapy ; follicular lymphoma ; progression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Among the 566 patients with follicular lymphomas (FL)included in the GELF 86 prospective trials from October 1986 to September1995, 372 with progressive/relapsing disease were analyzed retrospectively toidentify prognostic factors at first relapse. Patients and methods:For progressive FL, patients received mono-(22%) or polychemotherapy (78%) followed by high-dose therapy(HDT) with ASCT for 83 patients (22%). The median time toprogression from initial treatment was 23 months (range 3–102 months)and 24% of documented patients (52 of 217) had histologicaltransformation (HT). Salvage therapy produced an overall response in64% of patients and the five-year survival from progression was42%. Results:For patients who underwent HDT with ASCT compared tostandard treatment, five-year freedom from second failure was at 42%vs. 16% (P = 0.0001) and five-year survival was58% vs. 38% (P = 0.0005), respectively. Thebenefit of HDT and ASCT remained if we consider only patients less than 65years (five-year survival at 60% vs. 40%; P =0.001). Multivariate analysis of parameters significant according tounivariate analysis found that no ASCT at first progression, age at relapse〉50 years, progression on-therapy were adversely significant onsurvival. Conclusions:HDT with ASCT compared to standard treatmentprolonged remission and survival after first progression of FL patients.
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  • 30
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; chemotherapy ; colorectal cancer ; cost/effectiveness analysis ; irinotecan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:It has been shown that irinotecan is superior toinfusional 5-fluorouracil (5-FU) in patients with advanced colorectal cancerafter 5-FU failure. In a recent trial, median survival was 10.8 months forpatients treated with irinotecan, compared to 8.5 months in patients receivinginfusional 5-FU. Considering the statistically significant but clinicallyrelatively small advantage of irinotecan over 5-FU, cost effectiveness shouldalso be part of treatment decision. Purpose:To relate the costs of each management approach tooverall survival in patients with metastatic colorectal cancer. Patients and methods:The healthcare costs and medical benefits(treatment-added survival) of second-line chemotherapy in patients (infusional5-FU: 129, irinotecan: 127) were compared. Data on overall survival were drawnfrom a multicenter randomised trial that compared infusional 5-FU (continuousinfusion, AIO, or LV5-FU2 regimens) to irinotecan alone. Costs were derivedfrom the accounting system in two university hospitals in Paris, France. Results:The range in total healthcare costs was 14,135 to 12,192US$ patient between management approaches, with irinotecan chemotherapycosting most and 5-FU-continuous infusion least. If survival was included asa treatment benefit, the cost-effectiveness ratio of irinotecan over 5-FUranged from 9,344 to 10,137 US$ per year of added survival. Conclusions:The least expensive management for metastaticcolorectal was 5-FU infusion but the additional cost of irinotecan wasbalanced by the added months of survival, with a cost-effectiveness ratioclose to that of other cancer treatments.
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  • 31
    ISSN: 1569-8041
    Keywords: chemotherapy ; esophageal cancer ; gemcitabine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:There were approximately 12,500 cases of esophageal carcinoma diagnosed in the US in 1992 and 12,200 deaths. The impact of chemotherapy on patients with metastatic disease is marginal with a median survival of only five months. Gemcitabine (LY188011,2,2,–difluorodeoxycytidine: dFdC), an analog of cytosine arabinoside (ara-C), is a pyrimidine antimetabolite. Gemcitabine has shown interesting clinical activity in initial phase II clinical trials in a variety of malignancies, including the aerodigestive malignancies, squamous-cell carcinoma of the head/neck and both non-small-cell and small-cell lung cancer. Patients and methods:A total of 21 patients with chemotherapy-naïve metastatic esophageal carcinoma were entered. Nineteen patients were evaluable for toxicity and seventeen patients were evaluable for response. Gemcitabine was administered intravenously at 1250 mg/m2 over 30–60 minutes on days 1, 8, and 15 followed by 1 week of rest. This four-week schedule defined a cycle of treatment. Patients may have received a maximum of six cycles. Results:Gemcitabine was well tolerated with minimal non-hematologic toxicity and grade 3–4 anemia, granulocytopenia, and thrombocytopenia occurring in 10.5%, 21%, and 0% of patients, respectively. No responses were seen in the seventeen evaluable patients. Conclusions:At the dose and schedule studied it would appear that gemcitabine has no activity in patients with chemotherapy-naïve esophageal carcinoma.
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  • 32
    ISSN: 1433-0385
    Keywords: Keywords: Inguinal hernia ; Plug-and-patch repair ; Results ; Quality of life ; Geriatric ; Elderly. ; Schlüsselwörter: Leistenhernie ; Plug-und-Patch-Reparation ; Ergebnisse ; Lebensqualität ; geriatrisch ; älter.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Im Rahmen einer prospektiven Beobachtungsstudie wurden die perioperativen Ergebnisse der Plug-und-Patch-Reparation bei Patienten ≥ 65 Jahre untersucht und zusätzlich bei 34 konsekutiven Patienten die Lebensqualität vor und 3 Monate postoperativ standardisisiert mit Hilfe der Short Form (SF) 36 – einem validierten Lebensqualitätsbogen – erhoben. Von August 1994 bis Februar 1999 wurden 147 Patienten mit einem Durchschnittsalter von 73 ± 5 Jahren (65–92 Jahre) in der Plug-und-Patch-Technik zumeist in Lokalanaesthesie (LA: n = 124; 84 %, ITN: n = 23; 16 %) operiert. Die präoperativen Risikofaktoren waren vor allem Alkoholkonsum, Hypertonus, Diabetes mellitus, coronare Herzerkrankung, Nikotinkonsum, cerebrale Erkrankungen, Hyperlipidämie und pulmonale Erkrankungen. Nach anaesthesiologischer Einschätzung bestand in der Mehrzahl ein Stadium ASA II (ASA I: n = 14; 9 %, ASA II: n = 82; 56 %, ASA III: n = 51; 35 %). Die durchschnittliche Operationszeit betrug 41 ± 17 Min. (26–73). Intraoperative Komplikationen traten nicht auf, postoperative Komplikationen bestanden vor allem in oberflächlichen Wundhämatomen (n = 6; 3,7 %), und -infektionen (n = 1; 0,6 %), Seromen (n = 7; 3,8 %), Harnverhalt (n = 3; 1,8 %) sowie ilioinguinalem Schmerzsyndrom (n = 3; 1,8 %). Der postoperative Schmerzmittelbedarf betrug 4,9 ± 1,8 g Novalgin®über durchschnittlich 4 ± 3 Tage. Die Dauer des postoperativen Klinikaufenthaltes lag bei 2 ± 1 Tagen, die Einschränkung alltäglicher Verrichtungen bei 6 ± 3 Tagen. Bei der klinischen Nachuntersuchung ergab sich in allen Fällen ein regelrechter Befund ohne Hinweis auf ein Rezidiv oder Spätkomplikationen. Bei der Lebensqualität zeigte sich 3 Monate postoperativ eine signifikante Verbesserung (p 〈 0,05) in den Dimensionen: physische Funktion, Schmerz, Vitalität und soziale Funktion im Vergleich zu den präoperativen Werten. Tendentiell günstiger aber nicht signifikant waren postoperativ die Dimensionen Rolleneinschränkung sowie psychische und globale Gesundheit.
    Notes: Abstract. In a prospective study the perioperative results of plug-and-patch repair were investigated in patients ≥ 65 years, and quality of life was assessed using the SF36 preoperatively and 3 months after the procedure in 34 consecutive patients. From August 1994 to February 1999 147 patients with a mean age of 73 ± 5 years (65–92 years) were operated on using the plug-and-patch technique, mostly under local anesthesia (LA: n = 124, 84 %, ITN: n = 23, 16 %). Preoperative risk factors were alcohol consumption, hypertonus, diabetes mellitus, ischemic heart disease, smoking, cerebrovascular disease, hyperlipidaemia and pulmonary disease. Most of the patients were ASA II (ASA I: n = 14, 9 %, ASA II: n = 82, 56 %, ASA III: n = 51, 35 %). No intraoperative complications occurred, postoperative complications consisted of superficial wound hematoma (n = 6, 3.7 %) and infection (n = 1, 0.6 %), seroma (n = 7, 3.8 %), urinary retention (n = 3, 1.8 %) and ilioguinal pain syndrome (n = 3, 3.8 %). The total amount of postoperative analgesic consumption was 4.9 ± 1.8 g Novalgin for about 4 ± 3 days. The duration of postoperative hospitalization was 2 ± 1 days and limitation of daily activities 6 ± 3 days. Clinical examinations after 3 months revealed no recurrence or late complications. Investigation of quality of life showed a significant improvement in the SF36 domains of physical activity, pain, vitality, and social functioning after the operation. No significant change was observed for physical, emotional, and global health.
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  • 33
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    Der Chirurg 71 (2000), S. 1132-1137 
    ISSN: 1433-0385
    Keywords: Schlüsselwörter: Polytrauma ; Lebensqualität ; demographische Prädikatoren ; therapieabhängige Prädikatoren. ; Keywords: Multiple trauma ; Quality of life ; Demographic factors ; Injury related factors.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract. This study investigated multiple trauma patients, who were injured between 1991 and 1995 and treated in our department. The aim of this study was to identify the determinants of quality of life after multiple trauma. From a total of 186 patients 173 (93 %) were examined. The patients were asked to rate their quality of life according to the Nottingham Health Profile (NHP) and to a visual analogue scale (VAS). The VAS and the NHP isolated the age of the patients, the duration of artificial respiration, and the duration of rehabilitation as the predictors for a reduced overall quality of life. These results show that quality of life after multiple trauma not only depends on the severity of injury but also on demographic and psychosocial factors.
    Notes: Zusammenfassung. Ziel dieser Studie war es, Prädikatoren zu identifizieren, die die erreichbare Lebensqualität polytraumatisierter Patienten nach Abschluß ihrer klinischen und rehabilitativen Therapie determinieren. Es wurden 173 Patienten nachuntersucht, die in den Jahren 1991–1995 ein Polytrauma per definitionem erlitten hatten. Die posttraumatische Lebensqualität der Patienten wurde mit den international etablierten Meßinstrumenten Nottingham Health Profile (NHP) und einer visuellen Analogskala (VAS) bewertet. Über die VAS und den NHP ließen sich global das Alter der Patienten zum Zeitpunkt der Polytraumatisierung, die Beatmungsdauer und die Rehabilitationsdauer als hochsignifikante Determinanten der posttraumatischen Lebensqualität differenzieren. Diese Ergebnisse zeigen, daß die erreichbare Lebensqualität nach Polytrauma nicht nur von der Schwere der Verletzungen, sondern auch von vorbestehenden, therapeutisch nicht zu beeinflussenden demographischen und psychosozialen Daten abhängig ist.
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  • 34
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Morbus Parkinson ; Neuropsychologie ; Psychologische Tests ; Lebensqualität ; Keywords Parkinson's disease ; Neuropsychology ; Psychological tests ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In addition to the motor symptoms of Morbus Parkinson, a number of cognitive and emotional changes take place. The diagnosis of these concomitant symptoms has received increasing attention in research and clinical practice. Global rating scales offer economical advantages but generally do not satisfy the requirements of psychometric criteria, and they do not suffice in light of the multidimensional symptoms of the disease. Based on recent research results, recommendations from the CAPSIT protocol (Core Assessment Program for Surgical Interventional Therapies) for diagnosis of neurosurgically treated Parkinson's patients, and the restraints of everyday clinical work, we propose a standardized neuropsychological diagnostic routine. It includes diagnostic methods that are in use internationally and so timesaving and easily accessible that they can be considered suitable for routine diagnostics. Data comparison among various treatment centers can thus take place more easily. We have included only methods that differentiate well and whose test criteria offer a basis for thorough consultation as well as planning and evaluation of multidimensional therapy.
    Notes: Zusammenfassung Neben den motorischen Symptomen treten beim Morbus Parkinson eine Reihe kognitiver und emotionaler Veränderungen auf. Die Diagnostik dieser Begleitsymptome hat in den letzten Jahren nicht nur im Bereich der Forschung, sondern auch in der klinischen Praxis zunehmend an Bedeutung gewonnen. Globale Ratingskalen genügen trotz ihrer ökonomischen Vorteile in der Regel nicht den Anforderungen psychometrischer Testgütekriterien und werden der Multidimensionalität der Erkrankung nicht gerecht. Basierend auf dem aktuellen Stand der Forschung, den Empfehlungen des CAPSIT-Protokolls zur Diagnostik neurochirurgisch behandelter Parkinsonpatienten sowie den Erfordernissen der klinischen Praxis wird eine Testbatterie zur standardisierten neuropsychologischen Routinediagnostik vorgeschlagen. Sie umfasst diagnostische Verfahren, die zeitökonomisch, gut zugänglich und international verbreitet sind, um in der Routinediagnostik eingesetzt werden zu können und den Austausch zwischen verschiedenen Zentren zu vereinfachen. Es wurden nur Verfahren berücksichtigt, deren Differenziertheit und Testgüte Grundlage für eine fundierte Beratung sein können sowie solche, die für die Planung und Evaluation einer multidimensionalen Therapie geeignet sind.
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  • 35
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    Der Urologe 39 (2000), S. 527-529 
    ISSN: 1433-0563
    Keywords: Schlüsselwörter Interstitielle Zystitis ; Epidemiologie ; Inzidenz ; Prävalenz ; Lebensqualität ; Keywords Interstitial cystitis ; Epidemiology ; Incidence ; Prevalence ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Available data on the epidemiology of interstitial cystitis (IC) are heterogeneous. Its prevalence ranges between 16 and 510 females/100,000 inhabitants and the incidence at 1.2–2.6/100,000 females with a mean age of 42–52 years. The disease tends to affect women (female:male ratio 9–10:1) and Caucasians (〉90%). The quality of life of patients suffering from IC is reduced to a significant degree in almost every aspect (work, social events, leisure activities). Financial expenses (medical as well as economical) associated with the disease are considerable. There is an enormous need to promote IC education and research in order to support affected patients effectively in the future.
    Notes: Zusammenfassung Die vorliegenden Daten zur Epidemiologie der interstitiellen Zystitis sind sehr heterogen. Die Prävalenz beträgt 16–510 Frauen/100.000 Einwohner, die Inzidenz liegt zwischen 1,2–2,6 /100.000 Frauen mit einem mittleren Alter bei Diagnosestellung von 42–52 Jahren. Die Geschlechterverteilung bevorzugt das weibliche im Verhältnis zum männlichen Geschlecht (9–10 Frauen/1 Mann) mit einer ethnischen Bevorzugung der Kaukasier (〉90%). Die Lebensqualität der betroffenen Patienten ist in fast allen Lebensbereichen (Arbeit, Soziales, Freizeit) signifikant eingeschränkt. Die Kosten (sowohl medizinisch als auch volkswirtschaftlich) sind erheblich. Es besteht ein enormer Weiterbildungs- und Forschungsbedarf, um durch einen besseren Kenntnisstand den Patient(inn)en mit IC wirkungsvoll helfen zu können.
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  • 36
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    Der Orthopäde 29 (2000), S. 987-993 
    ISSN: 1433-0431
    Keywords: Schlüsselwörter Behinderungen ; Integration von Behinderten ; Lebensqualität ; Gesellschaftliche Einstellungen ; Sport ; Paralympiade ; Keywords Disabilities ; Integration of disabled persons ; Quality of life ; Social attitudes ; Sports ; Paralympics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract It is important to reflect back on the enormous changes that have taken place in society over the past century that have affected the quality of life of disabled persons and societal attitudes towards disability. Although great progress has been made, these people remain marginalized and disadvantaged, and despite all the efforts of volunteers, professionals, and governments, we cannot categorically state that they are fully socially integrated. The term disability continues to carry an enormous stigma, and therefore it is important to examine the concept of social integration and the issues around it as they affect disabled persons and the role of the International Paralympic Committee (IPC) movement in achieving this end.
    Notes: Zusammenfassung Nach Ablauf des letzten Jahrhunderts ist es wichtig auf die enormen gesellschaftlichen Veränderungen zurückzublicken und darauf, wie dieser Wandel die gesellschaftlichen Einstellungen gegenüber Behinderungen und die Lebensqualität von Behinderten verändert hat. Obwohl große Fortschritte gemacht wurden sind Behinderte immer noch eine benachteiligte Randgruppe; trotz aller Anstrengungen von Freiwilligen, Fachpersonal und Regierungen kann man noch nicht behaupten, dass sie voll gesellschaftlich integriert sind. Der Begriff “Behinderung” beinhaltet weiterhin ein großes Stigma. Deshalb ist es wichtig, das Konzept und die verschiedenen Aspekte der sozialen Intergration von Behinderten zu prüfen und die Rolle des Internationalen Paralympischen Kommittees (IPC) zur Verwirklichung dieser Ziele darzustellen.
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  • 37
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    Der Unfallchirurg 103 (2000), S. 371-374 
    ISSN: 1433-044X
    Keywords: Schlüsselwörter Knieendoprothese ; Lebensqualitätsgewinn ; Key words Knee endoprosthesis ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract From a group of 41 consecutive patients receiving an endoprosthetic knee replacement 35 patients underwent complete pre- and postoperative documentation of life quality in the short term follow-up. The comparison of pre- and postoperative life quality assessment with the SF-36 form showed significant differences on the 5% level for the categories “somatic pain” and “psychological wellness”. The parameter “somatic functionality” showed with a P-value of 0.0616 almost significant improvement. The other parameters also showed improved values without reaching statistical significance. In summary, after implantation of a total knee replacement an improvement of life quality can be documented.
    Notes: Zusammenfassung Aus einem Gesamtkollektiv von 41 nacheinander operierten Patienten konnten bei 35 Daten hinsichtlich der allgemeinen Lebensqualität im kurzfristigen Verlauf dokumentiert werden. Bei der Untersuchung der prä und post-operativen Lebensqualität mit Hilfe des SF-36-Scores zeigten sich auf dem 5-%-Niveau eine signifikante Verbesserung in den Kategorien “Körperliche Schmerzen” und “psychisches Wohlbefinden”. Mit einem P-Wert von p = 0,0616 kann eine fast signifikante Verbesserung in der körperlichen Funktionsfähigkeit konstatiert werden. Weitere 5 untersuchte Unterpunkte zeigten keine signifikante Verbesserung, jedoch bessere Werte bei den errechneten Mittelwerten. Zusammenfassend ist festzustellen, daß die Implantation einer Knieendoprothese zu einem deutlichen Gewinn in der Lebensqualität des kranken Menschen führt.
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  • 38
    ISSN: 1437-7772
    Keywords: Key words Gastric carcinoma ; Isolated hepatic recurrence ; Arterial infusion therapy ; Low-dose CDDP and continuous 5-FU ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients with metachronous liver metastasis after curative resection of gastric carcinoma generally have a poor prognosis, even when recurrence is confined to the liver. We report a patient in whom hepatic arterial infusion therapy with bolus low-dose cisplatin (CDDP) and continuous 5-fluorouracil (5-FU) was effective against large metastases confined to the liver. An 83-year-old man was admitted with huge liver metastases from gastric carcinoma. Intra-arterial bolus injection of low-dose CDDP (5 mg) and continuous intra-arterial infusion of 5-FU (250 mg/day for 7 days) was started. After four courses of this arterial infusion therapy, computed tomography scans revealed shrinkage of the liver metastases. He was followed-up as an outpatient and continued to receive the arterial infusion therapy once every 4 weeks. Throughout the course of the chemotherapy, a partial response of the liver metastases was maintained. The patient had an improved quality of life after starting the chemotherapy, and he survived for 16 months from the commencement of the therapy. Arterial infusion therapy with bolus low-dose CDDP and continuous 5-FU may be recommended for patients with isolated hepatic recurrence of gastric carcinoma.
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  • 39
    ISSN: 1433-8726
    Keywords: Key words Bladder neoplasm ; Quality of life ; QLQ-C30 ; Cystectomy ; Ileal conduit ; Orthotopic neobladder ; Urinary diversion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The impact of bladder removal and urinary diversion for patients' everyday life is largely unknown. The aims of this study were to compare subjective morbidity of ileal neobladder to the urethra versus ileal conduit urinary diversion and to elucidate its influence on quality of life. A total of 102 patients who underwent cystectomy due to a bladder malignancy were included in the study. In 69 patients (67.6%) an orthotopic neobladder and in 33 patients (32.4%) an ileal conduit was performed as urinary diversion. The compliance was 99% and mean follow-up was 37 months. All patients completed two retrospective quality of life questionnaires, namely the QLQ-C30 and a questionnaire developed at our institution to ask for urinary diversion specific items. The questioning and assessment was performed by non-urologists. The results obtained from the validated (QLQ-C30) and our own specially compiled questionnaire clearly demonstrate that patients with an orthotopic neobladder are more able to adapt to the new situation than patients with an ileal conduit. In addition, neobladder to the urethra improves the quality of life because it improves self-confidence, causes better rehabilitation as well as the restoration of leisure, professional, travelling, and social activities, and reduced risk of inadvertent loss of urine. For example, 92.8% of neobladder patients did not feel handicapped at all, and 87% did not feel sick or ill, in contrast to 51.5% and 66.7% of ileal conduit patients, respectively. Of the neobladder patients, 74.6% felt absolutely safe with the urinary diversion in contrast to 33.3% in the ileal conduit group. Only 1.5% of neobladder patients had wet clothes caused by urine leakage during the day, versus 48.5% of ileal conduit patients. Moreover, 97% of our neobladder patients would recommend the same urinary diversion to a friend suffering from the same disease, but only 36% of ileal conduit patients would do so. These results demonstrate that the quality of life is preserved to a higher degree after orthotopic neobladder than after ileal conduit urinary diversion.
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  • 40
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    European journal of pediatrics 159 (2000), S. 268-272 
    ISSN: 1432-1076
    Keywords: Key words Glycogen storage disease type 1b ; Portacaval shunt ; Ferrit MRI of liver adenoma ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In two girls with glycogen storage disease (GSD) type 1b, terminolateral portacaval shunt (PCS) with partial circular resection of the lobus quadratus of the liver was performed at the age of 12 and 10 years, respectively. At that time, the patients had a height of −3.1 and −1.7 SDS, respectively. PCS resulted in a spectacular growth spurt of 35 cm within the first 5 years after surgery in both of them. As first sign of puberty, breast enlargement started 2.5 years after PCS in both patients. Improved glucose tolerance was evidenced by increased levels of blood glucose and insulin after PCS. Diet with raw cornstarch (CS), 2g/kg body weight four times daily, was started 8 years after PCS in patient 1, but initiated with nightly gastric feeding at the age of 2 years in patient 2, 8 years before PCS. Treatment with recombinant granulocyte colony-stimulating factor (rhGCSF), 6 μg/kg body weight every 36–48 h, was started 20 years after PCS in patient 1, but only 1 month before PCS in patient 2. Progressive development of up to 7–8 liver adenomas was observed after PCS, but without conclusive signs of malignancy on Ferrit MRI. The PCS is still open 23 and 7 years after PCS, respectively. Terminolateral PCS with partial circular resection of the lobus quadratus of the liver associated with dietary control and rhGCSF might still have a place in the treatment of GSD type 1b because it improves the tolerance to fasting and the quality of life and moreover yields excellent metabolic control. Conclusion Treatment of glycogen storage disease type 1b by portacaval shunt might be considered in patients with height-for-age below the 3rd percentile occurring in spite of dietary control, or before considering liver transplantation which, if necessary, can still be performed after shunt surgery.
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  • 41
    ISSN: 1432-1459
    Keywords: Key words Motor neurone disease ; Amyotrophic lateral sclerosis ; SF-36 ; Carer Strain Index ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The measurement of functioning and well-being from the perspective of the patient has in recent years become central to the assessment of health and the evaluation of treatment regimes. The past decade has seen an enormous growth in the application of measures designed to assess quality of life in a vast array of medical specialities. However, the use of such measures in neurology has been relatively limited, and this has certainly been the case in amyotrophic lateral sclerosis (ALS). The European ALS Health Profile Study is a longitudinal survey of patients diagnosed with ALS or other motor neurone diseases in which patients are aksed to complete questionnaires concerning their subjective health status. Data from clinical assessments are also collected. It is intended that the information collected will provide more systematic and detailed evidence of the impact of the disease from the perspective of the patient. This contribution documents results from baseline assessment obtained from data supplied by clinicians, carers and patients themselves. Three outcome measured are assessed in this paper: the SF-36, a generic measure of well being and functioning, the ALS Functinal Rating Scale and the Carer Strain Index. The evidence presented here suggests that these measures provide a meaningful and valid picture of the impact of the disease. The data indicate that ALS has substantial adverse effects both upon the functioning and well being of patients and carers, as well as an association between the emotional health status of patients and carers, and between the physical health status of patients and carers.
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  • 42
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    Archives of gynecology and obstetrics 264 (2000), S. 51-53 
    ISSN: 1432-0711
    Keywords: Key words Self-expanding metallic endovascular stents ; Endometrial cancer ; Iliac vein thrombosis ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  There are few cases, to our knowledge, that report the successful treatment of iliac venous stenosis due to gynecologic malignancies with the use of self- expanding metallic endovascular stents. Our patient, who had right lower limb edema, had iliac lymph node metastases which caused iliac vein stenosis by direct invasion from endometrial cancer. The patient was not considered to be a good surgical candidate. A 10-mm diameter self-expanding metallic endovascular stent was placed in the external iliac vein. The patient’s symptoms of right lower limb edema improved dramatically, and she was discharged at 3 weeks after stent placement. The patient had no further symptoms, with continued resolution of the right leg edema during the 10 months following stent placement, at which time she died from the primary disease. The treatment to this patient with a self-expanding metallic endovascular stent proved to be very efficacious and less stressful than direct venous reconstruction or femorofemoral venous bypass grafting. In addition, this procedure dramatically improved the patient’s quality of life.
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  • 43
    ISSN: 1433-7339
    Keywords: Key words Cancer ; Fatigue ; Depression ; Symptom management ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Fatigue is one of the most frequent symptoms in cancer patients. However, the precise causes of this fatigue are still unknown, and this situation makes it difficult to combat the problem. The present study was conducted to investigate factors correlated with fatigue in disease-free breast cancer patients. A group of 134 randomly selected ambulatory breast cancer patients who had undergone successful surgical treatment participated. They completed the Cancer Fatigue Scale, the Hospital Anxiety and Depression Scale, the Mental Adjustment to Cancer Scale, and an ad hoc questionnaire detailing physical symptoms, social support, and demographic variables at home and returned them by mail the following day. Multiple regression analysis revealed that fatigue was significantly correlated with dyspnea, insufficient sleep, and depression, and that these three variables accounted for a total of 46% of variance in fatigue. Factors concerned with the cancer and treatment, such as disease stage, lymph node metastasis, number of days since operation, past intravenous chemotherapy, radiotherapy, current use of fluoropyrimidine compounds, and current use of tamoxifen citrate were not correlated with fatigue. The results suggest that fatigue in this population is determined by current physical and psychological distress rather than by the cancer itself and prior cancer treatments, and that the management of dyspnea, insomnia, and depression might be important in reducing fatigue in this population.
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  • 44
    ISSN: 1433-8491
    Keywords: Key words Obsessive-compulsive disorder ; Subclinical OCD ; Epidemiology ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Despite the worldwide relevance of obsessive-compulsive disorder (OCD) there are considerable differences in prevalence rates and gender ratios between the studies and a substantial lack of prevalence data on subclinical OCD. Moreover, data on quality of life and on psychosocial function of subjects with OCD and subclinical OCD in the general population are missing to date. Methods: German versions of the DMS-IV adapted Composite International Diagnostic Interview were administered to a representative sample of 4075 persons aged 18–64 years living in a northern Germany region. Specific DSM-IV based criteria for subclinical OCD were used. Results: The life-time prevalence rates for OCD and subclinical OCD were 0.5% and 2%, respectively. Twelve month prevalence rates were 0.39% and 1.6%, respectively. The gender female:male ratio was 5.7 in OCD and 1.2 in subclinical OCD. In various measures of psychosocial function and quality of life, OCD and subclinical OCD were significantly impaired. However, subclinical OCD subjects did not visit mental health professionals more often than controls. Conclusion: Due to different epidemiological characteristics subclinical OCD might represent a syndrome distinct from OCD which is also associated with significant impairments in personal and interpersonal functions and in quality of life.
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  • 45
    ISSN: 1569-8041
    Keywords: breast cancer ; carboplatinum ; chemotherapy ; continuous 5-fluorouracil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We performed a trial using the combination of epirubicin 50mg/m2/day 1, carboplatinum AUC 5/day 1 and continuous5-fluorouracil (5-FU) 200 mg/m2/day (every 4 weeks for6 months) to confirm the efficacy and low toxicity profile of thisregimen in breast cancer. In 51 patients with metastatic(n = 33) or locally advanced (n = 18)breast cancer the overall response rate was 86% (95% confidenceinterval (95% CI): 73%–94%): 94% in locallyadvanced and 81% metastatic disease. Grade 3–4 toxicity was low:4% of patients presented with febrile neutropenia, 16% withsevere palmar-plantar syndrome, 10% with Port-a-cath thrombosis. This study confirms the high efficacy of infusional 5-FU-based regimens andjustifies further research into novel promising oral 5-FU derivatives.
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  • 46
    ISSN: 1569-8041
    Keywords: chemotherapy ; intra-arterial ; liver metastasis ; unresectable pancreatic cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:A phase II trial of a new intra-arterial chemotherapyregimen for unresectable pancreatic cancer (UPC). Patients and methods:Ninety-six patients with UPC were treatedwith intra-arterial chemotherapy at three-weekly intervals. The schedule usedwas FLEC: 5-fluorouracil 1000 mg/m2, folinic acid 100mg/m2, carboplatin 300 mg/m2; epirubicin 60mg/m2. Results:The overall response rates by CT-scan evaluation were:15% partial response (PR), 44% stable disease (SD), 17%progressive disease (PD). The overall median survival was 9.9 months, and 10.6and 6.8 for UICC stage III and IV, respectively. Pain reduction occurred in42% of patients. A weight gain 〉7% from baseline occurred in8% of patients. A total of 341 courses of FLEC were administered. Grade3–4 hematological toxicity was seen in 25% of patients;ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; andgrade 3 alopecia in 16%. One sudden death, a pre-infarction angina, anda transitory ischemic attack were observed. The only complication related tothe angiographic procedure was an intimal dissection of the iliac artery. Conclusions:The intra-arterial FLEC regimen was well toleratedand active. It requires only one day of hospitalization. Efficacy could onlybe assessed in a randomized study against a gemcitabine containing regimen.
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  • 47
    ISSN: 1569-8041
    Keywords: chemotherapy ; combination ; etoposide ; ifosfamide ; ovarian cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The prognosis of platinum resistant ovarian cancer isvery poor and the treatment of choice has not been clearly defined. Patients and methods:We conducted a phase II study with thecombination of ifosfamide i.v. at 2.25 g/m2 (days 1, 2) andetoposide per os at 100 mg daily (days 1–10) every four weeks. To beeligible for the study patients had to be resistant to platinum and paclitaxelpretreated. Results:Forty-one patients entered the study. The median intervalfrom the previous chemotherapy was 3.9 months. The median number of previouschemotherapeutic regimens was 2. Severe toxicities included neutropenia(41% of patients), leukopenia (29%) and thrombocytopenia(13%). Thirty-five patients are assessable for response. Nine patientsresponded (22% of the eligible, 26% of the assessable), four ofthemdemonstrated complete response to chemotherapy (10% and 12%,respectively), while three patients demonstrated stabilization of theirprogressive disease. After a median follow-up of 18 months, time toprogression is 3 months (range 0.9–14.4), duration of response is 9months (2.5–11) and median survival is 13 months (2.5–37.4+). Conclusions:The combination of ifosfamide with oral etoposideappears to have significant but manageable toxicity and encouraging efficacyin platinum resistant ovarian cancer.
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  • 48
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    Annals of oncology 11 (2000), S. 11-16 
    ISSN: 1569-8041
    Keywords: chemotherapy ; gene therapy ; head and neck cancer ; immunotherapy ; radiotherapy ; recurrent ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Locoregional recurrence is the most common cause of failure after head andneck cancer surgery. It is a disease which causes significant morbidityespecially on speech and swallowing. There are many different treatmentsavailable including surgery, reirradiation and chemotherapy. However, none ofthese have produced any significant survival benefit. Because of this, therehas been considerable interest in the development of new biological therapiessuch as gene therapy and immunotherapy for this disease. The objectives ofthis article are to provide an overview of the currently available therapiesfor recurrent head and neck cancer including gene therapy and immunotherapy.Prevention of recurrent disease by the detection and treatment of minimalresidual disease is also discussed.
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  • 49
    ISSN: 1569-8041
    Keywords: chemotherapy ; hepatocellular carcinoma ; liposomal doxorubicin ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Pegylated liposomal doxorubicin has an enhancedefficacy and reduced toxicity compared with free doxorubicin. The efficacy andtoxicity of pegylated liposomal doxorubicin was investigated in patients withhepatocellular carcinoma. Patients and methods:Patients with histologically confirmed,locally advanced or metastatic hepatocellular carcinoma and a Karnofsky index〉60% were included in this prospective single-arm study. Exclusioncriteria were liver cirrhosis stage Child–Pugh C, previous chemotherapy,or chemoembolization. Pegylated liposomal doxorubicin was given in a dose of30 mg/m2 every three weeks until progression of disease. Afterinclusion of five patients the dose could be escalated to 40 mg/m2in absence of toxicity grade 3 and 4. Results:Sixteen patients were evaluable for response. Noobjective response was achieved. The median survival time was 140 days(95% confidence interval: 126–154 days). Treatment toxicitiesgrade ≥3 comprised increased liver enzymes in patients with preexistinggrade 1 or 2 elevation (n = 6), hematologic toxicity (n =5), and hypersensitivity (n = 2). Conclusions:Pegylated liposomal doxorubicin is not effective fortreatment of advanced hepatocellular carcinoma. The favorable toxicity profilewas confirmed even in patients with underlying liver disease.
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  • 50
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; non-small-cell lung cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty patients with chemotherapy-naïve advanced non-small-cell lungcancer (NSCLC) were given escalating doses of paclitaxel (150, 175, 200mg/m2) on day 1 in three consecutive cycles, together with a fixeddose of gemcitabine 1000 mg/m2 on days 1 and 8; cycles wererepeated every three weeks. The dose escalation of paclitaxel was feasible inthe majority of patients. Subsequently, 30 other NSCLC patients received adose of 200 mg/m2 paclitaxel with gemcitabine 1000 mg/m2in a phase II study. The major side effect was mild myelosuppression. Aresponse rate of 24% was achieved in 49 fully evaluable patients. Thisregimen proved to be safe and easy to administer on an out-patient setting,and constitutes now one of the arms of the current EORTC randomized study foradvanced NSCLC.
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  • 51
    ISSN: 1569-8041
    Keywords: BEACOPP ; chemotherapy ; dose intensification ; hematotoxicity ; Hodgkin's disease ; practicability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Evidence is recently accumulating that the novelBEACOPP (bleomycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C),vincristine (O), procarbazine (P), prednisone (P)) chemotherapy is a highlyeffective treatment for advanced stage Hodgkin's disease. Two dose variantsof BEACOPP are currently tested in a phase III randomized multicenter trialof the GHSG. To enable more extensive testing of BEACOPP we characterized itspracticability regarding schedule adherence, acute hematotoxicity and need forsupportive treatment. Patients and methods:Data of 858 patients (6592 therapy cycles)from 184 participating institutions were evaluated. Planned total drug dosesof the baseline variant (arm 1) were 80, 2400, 200, 5200, 11.2, 5600 and 4480mg/m2 for B, E, A, C, O, P and P, respectively. Compared to arm 1,the doses of E, A and C in the dose-intensified variant (arm 2) were escalatedby factor 2.0, 1.4, 1.92, respectively, using G-CSF assistance. Stepwise dosereductions were specified in case of dose-limiting toxicities. Both variantsare given in eight three-weekly courses. Results:Median dose adherence (dose actually given relative toplanned arm 1 dose) in arm 1 was 1.0 for all drugs. Relative dose escalationof E, A, and C actually maintained in arm 2 was 1.83, 1.37 and 1.77 (medians),respectively, and 70% of patients maintained elevated dose levelsthroughout the entire treatment. Dose-limiting toxicities occurred in25% of cycles in arm 2, most frequently due to leukocytopenia andthrombocytopenia. Time courses of leukocytes in arm 2 showed more severe butnot more prolonged leukocytopenia compared with arm 1. WHO grades 3–4infections were documented in 2.1% (arm 1) and 3.1% (arm 2) ofall cycles. Erythrocytes were transfused in 6% (arm 1) and 28%(arm 2), platelets in 〈1% (arm 1) and 6% (arm 2) of allcycles. Conclusions:Both BEACOPP schemes are practicable in a largemulticenter setting. Despite increased hematotoxicity, moderate doseescalation is safe for the majority of the patients with G-CSF assistance andstandard supportive treatment.
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  • 52
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    Annals of oncology 11 (2000), S. 1615-1616 
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; radiotherapy ; radiation myositis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 53
    ISSN: 1569-8041
    Keywords: advanced ovarian cancer ; chemotherapy ; docetaxel ; phase II trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:This phase II study was conducted to evaluate theefficacy and toxicity of docetaxel in Japanese patients with advanced ovariancancer. Patients and methods:Docetaxel was administered at a dose of 70mg/m2 intravenously to patients with platinum pre-treated advancedovarian cancer. Treatment was repeated every three weeks. No routinecorticosteroid premedication was given. Results:Ninety patients with advanced ovarian cancer were enteredand sixty were assessable for response. The overall response rate was28% in the assessable patients (95% confidence interval(95% CI): 17.5%–41.4%). CA125 responses were seenin 8 (24%) of 34 assessable patients for CA125 criteria. The 36platinum-refractory patients had a response rate of 25% compared with33% in the platinum-sensitive patients. The predominant toxicity wasneutropenia, with 86% of the patients experiencing grade 3 or 4.Hypersensitivity reactions occurred in 37% of the patients and were notlife threatening. Edema was mild and infrequent. Conclusion:Docetaxel at 70 mg/m2 demonstratedeffectiveness as a treatment of both platinum-sensitive andplatinum-refractory ovarian cancer patients, with a low incidence of severehypersensitivity reactions and edema.
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  • 54
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    Annals of oncology 11 (2000), S. 133-149 
    ISSN: 1569-8041
    Keywords: chemotherapy ; dose ; dose-density ; dose-intensity ; high-dose chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Shortening the interval between cycles is one meansof increasing the dose intensity of chemotherapy, and can be supported bybiological and mathematical rationales. Our objective was to assess theclinical relevance of the rapid repetition of regimens (so-called `dose-densechemotherapy') in various solid neoplasms. Design:The medical literature was reviewed in accord withMulrow's recommendations. Randomised studies comparing frequently-repeatedchemotherapy to standard regimens as well as open studies are described andcritically examined. Results:Dose-dense regimens were widely found to be feasible. In small-cell lung cancer, survival of patients receiving dose-denseregimens was better than that of patients treated by standard chemotherapy inthree trials, two of which reached significance, when these intensive regimensallowed better dose intensity. In poor-prognosis germ-cell tumors, a dose-dense regimen was not betterthan standard therapy, perhaps because of an excessively high toxicity-relateddeath rate. However, recent phase II studies have provided encouragingresults. In early breast cancer, the one published randomized study in the adjuvantsetting showed only a trend towards better disease-free survival innode-positive women receiving a weekly-repeated regimen. Two randomized trialsfailed to show any benefit in the neoadjuvant setting with a dose-denseregimen. No evidence of a benefit was provided in metastatic breast cancer. In advanced colorectal cancer, evidence of an improvement in survival withweekly or bi-weekly 5-FU–leucovorin compared to a classic monthlyschedule has recently been shown in two randomized trials, and dose-denseregimens are recognized as standard therapy in many countries. Phase II studies of dose-dense regimens have also shown high response ratesand long survival in many neoplasms, including Ewing's sarcoma, gestationaltrophoblastic disease, ovarian carcinoma and gastric cancer. Conclusions:A considerable amount of experience has been gainedwith frequently-repeated regimens. A few randomized trials have demonstrateda benefit for survival on standard chemotherapy in small-cell lung cancer andadvanced colorectal cancer. However, this benefit appears to be weak. Thecombination of dose-dense chemotherapy regimens with new anti-cancerstrategies based on our insights into the mechanisms of oncogenesis is achallenge on the eve of the millennium.
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  • 55
    ISSN: 1569-8041
    Keywords: carcinosarcoma ; chemotherapy ; thyroid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thyroid carcinosarcoma is a rare and aggressive thyroid tumor. Histologicalexamination of a tumor showed the characteristic of epithelial carcinoma andmesenchymal differentiation. We retrospectively analyzed the course of thepatient and reviewed the literature in which only 19 other cases aredescribed. Carcinosarcoma of the thyroid is a very aggressive tumor with aclinical course similar to anaplastic thyroid carcinoma. Survival is veryshort despite aggressive multimodal treatment.
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  • 56
    ISSN: 1569-8041
    Keywords: acute myeloid leukemia ; chemotherapy ; chronic lymphocytic leukemia ; immunosuppression ; second neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An increased incidence of different malignancies associated to chroniclymphocytic leukemia (CLL) has been reported. The association of CLL and acuteleukemia is a rare event described in 〈1% of CLL, the type of acuteleukemia being either from the lymphoid or more often from the myeloidlineage. The coexistence of acute myeloid leukemia (AML) and CLL in the samepatient has been occasionally reported. Most of these cases have beenassociated with the administration of chemotherapy or radioterapy for CLL,suggesting that the former may be a secondary leukemia. On the other hand, CLLcould precede, but could also be diagnosed at the same, or delayed time asAML, suggesting the presence of other leukemogenic factors. We describe theexceptional development of AML and lung cancer in a patient with previouslydiagnosed CLL in minimal residual disease status after fludarabine treatmentfollowed by autologous peripheral blood stem-cell transplantation.
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  • 57
    ISSN: 1569-8041
    Keywords: chemotherapy ; interferon ; transitionall-cell carcinoma ; urothelial tract
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Based on the favorable results of the combination5-fluorouracil (5-FU), cisplatin and interferon-α as second-line treatmentin advanced metastatic transitional-cell carcinoma of the urothelial tract aconfirmatory study was executed in a multicenter setting. Patients and methods:In this open label phase II study 43patients failing adequate previous chemotherapy were treated with IFN-α2b5 MU/m2 subcutaneously for 5 consecutive days starting on day 1 and22 simultaneous with 5-FU 500 mg/m2 daily as a continuous infusion.In between the same dose of IFN-α2b was given 3 times weekly with CDDP 25mg/m2 on days 1, 8, 15 and 22. This cycle was repeated every sixweeks. Results:In 40 eligible patients 5 PR were seen (12.5%;95% confidence interval (95% CI):4.1%–26.8%). The major toxicity was hematological. Twotoxic deaths were seen due to gastro-intestinal hemorrhage. Conclusions:In view of these results this combination can not berecommended as second line treatment for metastatic transitional-cellcarcinoma of the urothelial tract.
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  • 58
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    Annals of oncology 11 (2000), S. 1343-1347 
    ISSN: 1569-8041
    Keywords: chemotherapy ; Her2/neu ; indolent ; malignant ; palliative care ; secretory breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Secretory carcinoma of the breast is a rare and indolent tumour originallydescribed in children but occurring equally in the adult population. Theprincipal management problems following primary surgical treatment are localrecurrence and axillary lymph node metastases. Distant metastases areextremely rare. We present the case of a 27-year-old woman with pulmonary metastases froma secretory breast cancer treated by mastectomy and axillary lymph nodedissection 12 years previously. There was no response to chemotherapy; however, the patient remained aliveand active two years from presentation with metastatic disease and one yearfrom cessation of all cytotoxic chemotherapy. She eventually died ofrespiratory failure two and a half years after presentation. To our knowledge, this is only the fourth reported case of distantmetastases from secretory breast cancer and the second reported case in whichcurrent active chemotherapy has been used. We review the literature anddiscuss the apparent chemoresistance of this tumour including the lack ofmembrane staining for Her2/neu. In the absence of any proven effective chemotherapy we believe that symptomcontrol becomes the focus of management and offers patients with metastaticsecretory breast cancer the greatest chance of a functional and good qualityexistence.
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  • 59
    ISSN: 1569-8041
    Keywords: chemotherapy ; docetaxel ; gemcitabine ; non-small-cell lung cancer ; phase I trials ; taxanes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Docetaxel and gemcitabine are active in a broad rangeof malignancies. The objective of this phase I trial was to determine themaximally tolerated doses of the combination of docetaxel and gemcitabine. Patients and methods:Patients with advanced cancer, WHOperformance status 0–2, who had received up to one prior chemotherapyregimen were treated with gemcitabine on days 1 and 8 and docetaxel on day 8repeated every 21 days. Prophylactic ciprofloxacin was commenced on day 11 ofeach cycle and continued until the neutrophil count reached 1.0 ×109/l. G-CSF was not administered. Dose levels studied weredocetaxel/gemcitabine: 60/800, 60/1000, 75/1000, 75/1200, 85/1200 and 100/1200mg/m2. Results:Thirty-nine patients were entered and all were assessablefor toxicity. The highest administered dose level was 100 mg/m2docetaxel and 1200 mg/m2 gemcitabine with dose limiting toxicitiesof febrile neutropenia, grade 4 neutropenia ≥7 days, grade 4thrombocytopenia, grade 3 stomatitis and/or grade 3 fatigue in three out ofsix patients. Treatment was well tolerated (40 cycles) in the 10 patientstreated at the recommended dose level (85/1200) with only a single episode offebrile neutropenia and grade 3 or 4 non-hematologic toxicity was infrequent.There was no significant pulmonary toxicity. Responses were seen in a rangeof malignancies including non-small-cell lung cancer. Conclusions:The recommended dose level of 85 mg/m2docetaxel and 1200 mg/m2 gemcitabine has a favourable toxicityprofile and is suitable for further investigation in phase II trials. Thisnon-platinum containing regimen warrants further investigation as a potentialalternative to platinum containing regimens in non-small-cell lung cancer andother malignancies.
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  • 60
    ISSN: 1569-8041
    Keywords: cervical cancer ; chemotherapy ; phase I ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background.Cisplatin and paclitaxel are active in cervical cancerand both are able to potentiate the effects of radiotherapy. In this study weevaluated the maximum-tolerated dose (MTD) of paclitaxel in combination witha fixed dose of cisplatin when given weekly concurrently with pelvicradiotherapy to patients with carcinoma of the cervix uteri. Patients and methods:Eighteen patients with cervical cancer wereenrolled in this study. Cisplatin (30 mg/m2) and paclitaxel(starting dose 40 mg/m2; 5 mg/m2 escalation per level)were given on day 1 of radiotherapy and then weekly for six times.Radiotherapy was given to the pelvis with a four-field box technique for fivedays each week. Patients received 65 Gy in 1.8 Gy fractions. Cohorts of threepatients were enrolled at each level and three further patients were includedif one or two dose-limiting severe adverse events (SAE) were recorded. SAE wasdefined as grade 3 or 4 nonhematologic toxicity, excluding nausea or vomitingand alopecia, grade 4 neutropenia or thrombocytopenia, and prolonged (〉1week) neutropenia or thrombocytopenia. Results:Four levels were studied (paclitaxel 40, 45, 50, 55mg/m2) with three, five, four and six patients enrolled,respectively. The MTD of paclitaxel was found at 50 mg/m2/wk andcisplatin 30 mg/m2/wk. Diarrhea was the dose-limiting toxicity.Thirteen patients were evaluable for response: seven complete and five partialresponses were obtained with an overall response rate of 92.3%. Conclusions:The MTD of paclitaxel is 50 mg/m2/wk whenassociated to cisplatin 30 mg/m2/wk and concurrent pelvicradiotherapy. Diarrhea is the dose limiting side effect. Preliminary datasuggest that concurrent chemoradiotherapy with paclitaxel and cisplatin couldbe a very active treatment for patients with locally advanced carcinoma of thecervix.
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  • 61
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    Annals of oncology 11 (2000), S. 509-513 
    ISSN: 1569-8041
    Keywords: assessment ; chemotherapy ; eripheral neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 62
    ISSN: 1569-8041
    Keywords: advanced breast cancer ; chemotherapy ; gemcitabine ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine and vinorelbine have shown activity inbreast cancer. A phase II trial was initiated in order to evaluate theresponse rate (RR) and time to progression (TTP) of the combination of the twodrugs in patients with metastatic breast cancer progressing after first-linetaxane-based chemotherapy. Patients and methods:Thirty-one patients were treated with thecombination of gemcitabine 1000 mg/m2 days 1 + 8 and vinorelbine30 mg/m2 days 1 + 8. The cycles were repeated every three weeks. Results:Of 27 evaluable patients 1 (4%, 95%confidence interval (95% CI): 0.1%–19%) achievedcomplete remission (CR), five (18%; 95% CI:6%–38%) partial remission (PR), eleven (40%;95% CI: 22%–61%) stable disease and ten patientsprogressed. The median duration of response was six months (range 4–10+)and the median duration of disease stabilization was five months (range2–22+). With a median follow-up of 16 months (range 0.4–22+) themedian TTP was 3.5 months (range 0.4–22+) and the median survival was9.5 months (range 0.4–22+). Grade 3–4 toxicities weregranulocytopenia 15 patients (48%), rash 3 patients (10%),neuropathy 1 patient (3%) and thrombocytopenia 1 patient (3%).In conclusion the combination of gemcitabine/vinorelbine in the dosesadministered in this group of patients had a response rate of 22% andneeds to be further evaluated in metastatic breast cancer.
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  • 63
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    Annals of oncology 11 (2000), S. 927-937 
    ISSN: 1569-8041
    Keywords: brain lymphomas ; chemotherapy ; intrathecal chemotherapy ; methotrexate ; primary central nervous system lymphoma ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Primary central nervous system lymphomas (PCNSL) are aggressivemalignancies, exhibiting one of the worst prognoses among lymphomas. The besttreatment modality for PCNSL has not yet been identified. Several therapeuticquestions still remain unanswered, and some methodological pitfalls inclinical trials prevent definitive conclusions from being drawn. In thisreview, certain aspects of trial design as well as emerging therapeuticguidelines are analyzed, and future perspectives are discussed. In the vast majority of prospective trials, general criteria for treatmentof aggressive lymphomas were adopted, choosing primary chemotherapy (CHT)followed by radiotherapy (RT) as therapeutic modality. This strategy produceda five-year survival of 22%–40% in comparison to the3%–26% reported with RT alone. Systemic high-dosemethotrexate (HD-MTX) seems to be the most effective drug, producing aresponse rate of 80%–90% and a two-year survival of60%–65%. To date, the addition of other drugs atconventional doses have not consistently improved outcome. With a fewexceptions, any regimen without HD-MTX comprehensively performed no betterthan RT alone. In combined treatment, RT doses should be decided on the bases of responseto primary CHT and the number of lesions, and, until definitive conclusionsfrom well-designed trials are available, RT parameters should follow thewidely accepted principles used for other aggressive lymphomas. CHT asexclusive treatment, keeping RT for relapses or persistent disease, appearsto be an attractive strategy. However, the worldwide experience with thismodality is still limited, and corroborating data are needed. Intrathecal CHTstill has not found a defined role in PCNSL management. Preliminary data seemto indicate that adequate meningeal treatment with HD-MTX, but withoutintrathecal CHT, could also be suitable in positive-cerebrospinal fluidpatients. Future efforts should be addressed to identify new active drugs and moreefficient CHT combinations, to evaluate the efficacy of high-dose CHTsupported by autologous peripheral blood stem cells transplantation, and toclarify the impact of RT delay in complete responders, the usefulness ofintrathecal CHT, and the best management for elderly patients. The assessmentof impact of treatment on neuropsychological functions and quality of life isa mandatory endpoint in clinical trials.
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  • 64
    ISSN: 1569-8041
    Keywords: Charcot–Marie–Tooth disease ; chemotherapy ; hereditary motor and sensory neuropathy ; PMP22 ; vincristine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Severe up to life-threatening neuropathy has beenobserved in patients with hereditary neuropathies receiving vincristine. Case report:A 52-year-old female painter suffering fromhigh-grade non-Hodgkin's lymphoma (stage IVB) was treated with a total of 4mg of vincristine during two courses of CHOP chemotherapy (cyclophosphamide,vincristine, adriamycin, prednisone). At onset of treatment no neurologicalproblems were reported. There was good lymphoma response to chemotherapy. Atthe same time, however, the patient gradually developed dysphagia, dysarthria,muscular weakness of both lower and upper extremities, areflexia, paraesthesiaof the fingertips and bilateral sensory impairment of feet and lower legs.These symptoms continually worsened over a period of seven weeks until she wasunable to walk or to perform her work. Electrophysiological studies showedperipheral axonal and demyelinative sensorimotor neuropathy in correlation tohistological findings. Molecular analysis revealed 17p11.2 duplication typicalfor Charcot–Marie–Tooth disease IA. While continuing chemotherapywithout the use of vincristine the patient's neurologic symptoms slowlyrecovered within six months. Conclusion:Prior to administration of vincristine family andpatient history as well as physical examination should be performed carefullyto look for underlying hereditary neuropathy. For those patients with aclinical history or symptoms suggestive for CMT nerve conduction velocitystudies and on an individual base even molecular genetic analysis areneccessary to prevent serious neurologic complications.
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  • 65
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    Annals of oncology 11 (2000), S. 1523-1530 
    ISSN: 1569-8041
    Keywords: androgen-independent prostate cancer ; chemotherapy ; metastatic prostate cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background and purpose:A great number of clinical researchstudies have been reported in the field of chemotherapy for advancedandrogen-independent prostate cancer during the last ten years. The aims ofthe present review were to assess their impact on management of the diseaseand on survival of patients. Methods:The review of full published reports was facilited by theuse of a MEDLINE computer search. Results:Clinical research studies have focused on definingguidelines for eligibility criteria and accurate endpoints for patients to beenrolled onto clinical trials and developing new agents or combinationof drugs including estramustine phosphate. Any combination of currentchemotherapy has no impact on overall survival of patients. Among drugs indevelopment, only the promising activity observed with docetaxel deservesrandomized trials to assess its impact on survival. The major innovativeadvance of the 90s is the demonstration of the impact of chemotherapy(mitoxantrone + prednisone) on quality of life as compared to prednisonealone. A greater and longer-lasting improvement in quality of life along witha concomitant decrease in costs was observed. Conclusions:At the present time, chemotherapy should beconsidered as a palliative treatment in patients with symptomaticandrogen-independent disease. The enrollment of patients into clinical trialsdealing with quality of life as primary endpoint is strongly solicited. Astandard methodology should be used in phase II trials with a primary goal ofselection of agents which should progress to randomized trials using survivalas an endpoint. Hopefully new specific strategies targeted to reverse themolecular changes that underlie prostate tumorigenesis should rapidly impactthe multimodality management of AIPC in the third millenium.
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  • 66
    ISSN: 1569-8041
    Keywords: cancer ; chemotherapy ; pleuropulmonary blastoma ; PPB ; soft tissue sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pleuropulmonary blastoma (PPB) is a rare dysontogenetic tumor that usuallydevelops in the first decade of life and has been recognized as a distinctclinico-pathological entity different from the ordinary pulmonary blastoma ofadulthood. Since the tumor grows aggressively and tends to metastasize early,physicians have to be aware of late onset of symptoms and uncommonmanifestations. We report a case of PPB in a young adult and its recurrencein the pancreas after primary surgical treatment and adjuvant chemotherapy.Keeping in mind the moderate prognosis of PPB in children, accurate assessmentand treatment of PPB require a team approach of oncology, radiology andsurgery to establish new therapeutic guidelines in the future.
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  • 67
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    Annals of oncology 11 (2000), S. 217-220 
    ISSN: 1569-8041
    Keywords: chemotherapy ; Guillain–Barré syndrome ; lymphoma ; polyneuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe a case of Guillain–Barré syndrome (GBS) in apatient with non-Hodgkin's lymphoma (NHL). A 21-year-old woman with a newlydiagnosed stage IV high-grade lymphoma (precursor T-cell NHL according to theR.E.A.L. Classification) developed flaccid quadriparesis and bilateral facialdiplegia after three weeks of treatment with vincristine, daunorubicin,L-asparaginase and prednisolone. The clinical course and neurologicalexamination were consistent with GBS. Despite treatment with intravenousimmunoglobulins her neurological symptoms progressed. Plasmapheresis wastherefore initiated followed by intravenous immunoglobulins. After partialremission of neurologic symptoms, induction chemotherapy with cyclophosphamideand cytarabine was continued without any further complication. Three monthslater, the lymphoma was in complete remission. GBS has been described inHodgkin's disease and after bone marrow transplantation but is rare in NHL.In patients with NHL who develop neurological symptoms, drug toxicity andnervous system infiltration are the leading cause of neuropathology, but GBSshould be considered in the differential diagnosis.
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  • 68
    ISSN: 1569-8041
    Keywords: chemotherapy ; doxorubicin ; hepatocellular carcinoma ; liposome ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:There is lack of effective and safe chemotherapy foradvanced hepatocellular carcinoma. Polyethylene glycol-coated (pegylated)liposomal doxorubicin (PLD) has long circulation time and enhanced drugaccumulation in the tumor tissues. It has significant activity in Kaposi'ssarcoma, breast and ovarian cancers and the acute adverse effects of free drugare reduced. Patients and methods:A patient with advanced hepatocellularcarcinoma was treated with PLD and a pharmacokinetic study was performed.Initial serum total and direct bilirubin were 3.6 and 6.8 folds of uppernormal, respectively, and an indocyanine green clearance test at 15 minuteswas 26.3% (normal 〈 15%). Results:Compared to cases with normal liver function, increasedvolume of distribution of doxorubicin correlated with a large amount ofascites (P〈 0.05). The clearance of drug was unexpectedly higherthan in cases with normal liver function (P〈 0.05). According tothe pharmacokinetic studies, the disposition of PLD in this case has not beenretarded even in the presence of severe liver dysfunction. Only minimaltoxicities including grade 2 stomatitis and moderate leukopenia were observed.The tumor had a partial remission and the patient survived nine months afterPLD treatment. Conclusion:PLD could serve as a safe and effective treatment forhepatocellular carcinoma even in the presence of impaired liver function. Itsrole in treating advanced hepatocellular carcinoma is worthy of further study.
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  • 69
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; non-small-cell lung cancer ; phase II trial ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:The purpose of the present phase II trial was todetermine the efficacy and toxicity of vinorelbine–gemcitabine inpatients with advanced non-small-cell lung cancer (NSCLC). Patients and methods:From December 1997 to February 1999, 78chemotherapy-naive patients (median age 60 years, Karnofsky performance statusof 100, 90, 80 and 70 present in 5%, 41%, 36% and18% of the patients, respectively) with stage IIIB (17%) or IV(83%) NSCLC (65% adenocarcinomas, 22% squamous-cellcarcinomas, 10% large-cell carcinomas, 3% mixed-cell carcinomas)received 25 mg/m2 vinorelbine and 1200 mg/m2 gemcitabineon days 1, 8 and 15 of a four-week cycle. Results:In an intent-to-treat analysis, partial responses wereseen in 19% of the patients. The median duration of response was 4.4months. The median survival time was seven months and the one-year survivalrate was 32%. Myelosuppression was the main side effect with WHO grade3/4 neutropenia and thrombocytopenia in 35% and 11% of thepatients, respectively. Other side effects were usually mild to moderate. Conclusions:Vinorelbine–gemcitabine is active, welltolerated and easy to administer on an outpatient basis in advanced NSCLC.Thus a randomized comparison of this combination with platinum-based protocolsis warranted in patients with advanced NSCLC.
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  • 70
    ISSN: 1569-8041
    Keywords: chemotherapy ; colorectal cancer ; oxaliplatin ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Backround:Oxaliplatin is a novel platinum derivative, which,combined with 5-fluorouracil (5-FU), and folinic acid (FA), demonstratessynergistic activity in metastatic colorectal cancer (MCC). The HeCOGperformed a multicenter phase II study of a weekly oxaliplatin administrationschedule in patients with previously treated MCC to evaluate the antitumorefficacy and toxicity of this combination. Patients and methods:Eligible patients included those whorelapsed after or during chemotherapy with 5-FU and FA and/or irinotecan.Prior radiotherapy was accepted provided that measurable disease was outsidethe radiation fields. Other eligibility criteria included written informedconsent, a WHO performance status ≤2 and adequate bone marrow, liver andrenal function. Treatment consisted of Oxaliplatin 50 mg/m2 bytwo-hour intravenous (i.v.) infusion followed by FA 500 mg/m2(two-hour i.v. infusion) and 5-FU 2500 mg/m2 (24-hour continuousi.v. infusion) on days 1, 8, 15, 22, 29, 36. The regimen was repeated every50 days. Results:Thirty-two patients (Median age 61 years, range25–76) entered the trial. The majority (75%) had progressed afterreceiving first-line chemotherapy. Diarrhea was the main non-hematologic toxicity. More than half of thepatients (53%) developed grades 3 or 4 diarrhea. Due to this sideeffect only 29% of cycles were given with at least 90% of theplanned dose of 5-FU. Hematologic toxicity included grade 3 neutropenia andthrombocytopenia (10% for each), and grade 4 thrombocytopenia(3%). Two patients (6%) died of sepsis, one related toneutropenia and one due to urinary tract sepsis. Sixteen patients (50%)developed grades 1 and 2 neurotoxicity in the form of sensory neuropathy,which was mild and transient. The objective response rate was 13%(95% CI: 3%–29%). All four responses were partial.Twelve patients (38%) had stable disease and 8 (25%) progressivedisease. The median time to progression was three months and the mediansurvival was nine months from the start of therapy. The Kaplan–Meierestimated probability of one-year survival for the group as a whole was32%. Conclusions:The weekly administration of oxaliplatin with 5-FUand FA was associated with considerably less neurotoxicity than otherschedules. However, the high percentage of diarrhea suggests that a dosereduction of 5-FU in this regimen may result in better therapeutic synergy.
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  • 71
    ISSN: 1615-6722
    Keywords: Schlüsselwörter Koronare Herzerkrankung ; Perkutane transluminale Koronarangioplastie (PTCA) ; Angina pectoris ; Lebensqualität ; Anschlußheilbehandlung ; Key words Coronary artery disease ; Percutaneous transluminal coronary angioplasty (PTCA) ; angina pectoris ; Quality of life ; Rehabilitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background: Quality control becomes increasingly important in interventional cardiology. Since in most health care systems, clinical treatment of patients who underwent percutaneous transluminal coronary angioplasty (PTCA) is left to general practitioners, important information on the clinical long-term outcome is lost for the cardiologic centers. Aim of this study was to evaluate the clinical status of these patients 4 years after treatment with a PTCA at our institution. Patients and Methods: Inclusion criterion was the treatment with a PTCA within July 1, 1989 to June 30, 1991 (549 Patients). A questionnaire was sent to all patients (45±7 months after PTCA). Four time-points were defined: before PTCA (T1), directly after PTCA (T2), 3 months after PTCA (T3) and actual status (T4). Results: Questionnaires of 500/549 (91,1%) patients could be analyzed. One-hundred and fifteen patients (23%) had to undergo reinterventions: 69 (13.8%) had a re-PTCA and 46 (9.2%) patients an operative revascularization. At T4, 11.2% patients still had disturbing angina. Within the study period 35 patients (7%) died. Two-hundred and nineteen patients attended a rehabilitation institution. At T4, the amount of patients with little angina was not different comparing patients with/without the attendance of a rehabilitation institution (60.7% vs 66.4% p = 0.29). The rate of new pensioners after PTCA (n = 114 [22.8%] was higher in the group of patients who attended a rehabilitation (68 patients [13.6%] with vs 48 patients [9.2%] without attendance, p = 0.0036). The attendance of a rehabilitation institution, however, had positive effects on changes of the life stile and eating habits. Conclusions: This retrospective inquiry was found to be a useful tool (response rate 91.1%) for quality control in interventional cardiology. Important information concerning the quality of the interventions (low reintervention rate) and the long-term outcome of our patients (low rate with severe angina at T4) could be aquired.
    Notes: Zusammenfassung Hintergrund: Die Qualitätskontrolle gewinnt in der interventionellen Kardiologie zunehmend an Bedeutung. Da aber die Nachbetreuung von Patienten, die mit einer perkutanen transluminalen Koronarangioplastie (PTCA) behandelt wurden, meist durch die jeweiligen Hausärzte durchgeführt wird, gehen dem kardiologischen Zentrum wichtige Informationen hinsichtlich des klinischen Langzeitverlaufs verloren. Ziel dieser retrospektiven Studie war daher, den klinischen Status dieser Patienten vier Jahre nach der Behandlung mit einer PTCA an unserer Institution zu untersuchen. Patienten und Methode: Einschlußkriterium war die Behandlung mit einer PTCA im Zeitraum vom 1.7.1989 bis 30.6.1991 (549 Patienten). Zur Erhebung der Langzeitergebnisse (45±7 Monate nach PTCA) wurde den Patienten ein Fragebogen zugesandt. Vier Erhebungszeitpunkte wurden definiert: vor PTCA (T1), direkt nach PTCA (T2), drei Monate nach PTCA (T3) und zum Erhebungszeitpunkt (T4). Ergebnisse: Fragebögen von 500/549 (91,1%) Patienten kamen zur Auswertung. 115 (23%) Patienten mußten sich einer Reintervention unterziehen (PTCA: 69 Patienten [13,8%], aortokoronare Venen-Bypass-(ACVB-)Operation: 46 Patienten [9,2%]). Zu T4 hatten 11,2% Patienten stärkere Angina-pectoris-Beschwerden. 35 Patienten (7%) waren im Erhebungszeitraum verstorben. 219 Patienten (52%) nahmen an einer Anschlußheilbehandlung teil. Zu T4 waren diese Patienten nicht häufiger beschwerdefrei als Patienten ohne Anschlußheilbehandlung (60,7% vs. 66,4%, p = 0,29). Der Anteil der nach Intervention neu berenteten Patienten (n = 114 [22,8%] war in der Gruppe mit Anschlußheilbehandlung höher (68 Patienten [13,6%] mit Anschlußheilbehandlung vs. 46 Patienten [9,2%] ohne Anschlußheilbehandlung, p = 0,0036). Positiven Einfluß hatte die Teilnahme an einer Anschlußheilbehandlung auf Änderungen des Lebensstils und der Eßgewohnheiten. Schlußfolgerung: Diese retrospektive Befragung erwies sich als sinnvoll (Antwortrate 91,1%), um Daten zur Qualitätskontrolle zu erheben. Wichtige Informationen sowohl hinsichtlich der Qualität der Koronarinterventionen (niedrige Reinterventionsrate) als auch hinsichtlich des klinischen Langzeitverlaufs (niedriger Anteil von Patienten mit schwerer Symptomatik nach vier Jahren) konnten hierdurch gewonnen werden.
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  • 72
    ISSN: 1573-7276
    Keywords: ALCAM ; annexin II ; chemotherapy ; metastasis ; progression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Metastasis frequently occurs during and/or after chemotherapy resulting in failure. This suggests that inadequate chemotherapy promotes the emergence of more malignant tumor cells with metastatic potential. However, it is not determined how chemotherapy could promote the metastatic progression of tumor cells. In this study, we isolated highly metastatic clones from the tumors treated with ADR using an in vivo experimental model, in which non-metastatic tumor cells were inoculated s.c. in mice, treated with or without Adriamycin and then culture lines were re-established from the tumors. Then we isolated cDNAs for activated leukocyte cell adhesion molecule (ALCAM), osteopontin, and annexin II as candidates for metastasis-promoting genes with the use of a PCR-based subtraction method. Further we examined the metastatic potential of transfectants over-expressing ALCAM, osteopontin, or annexin II and combinations of them. Metastasis to the lung was observed in the mice where transfectants over-expressing ALCAM plus annexin II had been inoculated via tail vein. These results suggest that the over-expression of ALCAM and annexin II play a role in the metastatic progression after chemotherapy with ADR.
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  • 73
    ISSN: 1573-7284
    Keywords: GHQ-28 ; Ischaemic heart disease ; Mental health ; Quality of life ; SF-36 ; Validity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To assess the mental health of patients admitted to hospital with suspected ischaemic heart disease, by means of two instruments, the General Health Questionnaire (GHQ-28) and the MH (1–5) dimension of the SF-36 Health Survey Questionnaire, and to compare the psychometric properties of both questionnaires in this population. Methods: A study was conducted of 185 patients consecutively admitted to hospital with suspected ischaemic heart disease, classified into four groups: Acute Myocardial Infarctus (AMI), unstable angina, non-ischaemic cardiologies, and non-cardiological conditions. Their mental health was assessed by means of the GHQ-28 and the MH 1–5 sub-scales of the SF-36; the validity of the results were analysed by the association of each instrument with socio-demographic (age, sex, social class, and educational level) and clinical (co-morbidity, risk factors, diagnostic groups and background to the illness) variables. The correlation of each instrument with other sub-scales of the SF-36 was studied. The internal consistency was measured by Cronbach's α, together with the item-internal consistency and item-discriminant validity. Results: Of the population studied, 71.9% were males and the mean age was 60.2 years (SD: 10.4). The diagnosis for 33.5% was AMI and for 37.8% unstable angina. For all the variables studied, the scores in the two instruments were ordered in the same way, and were significantly worse for females and for the most disadvantaged social class. None of the scales discriminated in respect of the diagnostic group or the presence of comorbidity. However, a linear relationship was observed with risk factors. Cronbach's α was 0.95 for the GHQ-28 and 0.80 for the MH 1–5. Correlations with the other dimensions showed ranges of −0.35 to −0.61 for the GHQ-28 and of 0.26 to 0.61 for the MH 1–5. These were highest for the Vitality and Social Functioning sub-scales in both instruments. Conclusions: The subjective perception of mental health is measured in a similar way by both the MH 1–5 scale of the SF-36 and the GHQ-28. However, since the MH 1–5 questionnaire is shorter, it should be administratively easier to introduce into routine cardiological practice.
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  • 74
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    Journal of neuro-oncology 47 (2000), S. 293-307 
    ISSN: 1573-7373
    Keywords: chemotherapy ; intramedullary ; spinal cord tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intramedullary tumors are rare, accounting for only about 4% of all CNS neoplasms. Although surgery represents the most effective treatment, recurrence may occur. As a large proportion of intramedullary malignancies occur in children, who are more sensitive to the deleterious effects of irradiation, chemotherapy assumes an important role. This article describes the most common intramedullary tumors and the role of chemotherapy.
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  • 75
    ISSN: 1573-7373
    Keywords: malignant glioma ; chemotherapy ; anthracyclines ; KRN8602 (MX2) ; phase II study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract KRN8602 (MX2) is a newly developed morpholino anthracycline that crosses the blood–brain barrier where it becomes distributed in brain tissue after intravenous administration. This morpholino anthracycline has been found to be effective against human glioma cells and the intracerebrally transplanted tumors in vivo. We performed a phase II trial using KRN8602 as a single agent in malignant glioma patients who had not received prior adjuvant therapy. The 13 patients (5 glioblastomas, 7 anaplastic astrocytomas and 1 malignant oligodendroglioma) enrolled received at least 1 cycle of KRN8602 at 35 mg/m2/day in 3–4 week intervals by intravenous bolus. Ten of these patients could be evaluated for response, and 13 for toxicity. Three patients (1 glioblastoma and 2 anaplastic astrocytomas) demonstrated a complete response (3/10, 30%). Concerning side effects, myelosuppression was moderately severe, with 30.7% of patients developing grade 3 leukopenia. Severe nausea/vomiting was observed in 69% of the patients, however, cardiotoxicity was not observed. The results indicate that KRN8602 demonstrated modest activity against malignant glioma with relatively severe, but manageable toxicity. Further assessment of the efficacy and toxicity of KRN86O2 against malignant glioma may be worthwhile.
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  • 76
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    Journal of neuro-oncology 49 (2000), S. 231-234 
    ISSN: 1573-7373
    Keywords: treosulfan ; chemotherapy ; malignant glioma ; myelosuppression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Treosulfan is a bifunctional alkylating prodrug with activity against various solid tumors. To improve the outcome for patients with recurrent malignant glioma, we assessed the efficacy of intravenous treosulfan (6–10 g/m2 4-weekly) as salvage therapy for patients with recurrent or progressive glioblastoma (GB, n = 14) or anaplastic astrocytoma (AA, n = 2). All patients had prior involved-field radiotherapy and adjuvant nitrosourea-based chemotherapy. A total of 56 cycles were administered. Tumor responses were assessed radiologically and clinically prior to each cycle. All patients were assessable for toxicity, response and survival. There were no complete or partial responses (CR, PR). Two patients progressed after the first cycle, 14 patients had initially stable disease (SD). Median progression-free survival was 3.25 months for the GB patients. Five patients were progression-free at 6 months (30%), including the 2 AA patients. The 2 AA patients are stable at 22 months. Myelosuppression was the dose-limiting toxicity in this cohort of nitrosourea-pretreated patients. Treosulfan has modest activity in patients with recurrent malignant glioma. Further evaluation of treosulfan in chemonaive malignant glioma patients is warranted.
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  • 77
    ISSN: 1573-7373
    Keywords: DTIC ; dacarbazine ; recurrent gliomas ; brain tumors ; chemotherapy ; glioblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We conducted a randomized phase II study to determine the efficacy of dacarbazine (DTIC) in recurrent gliomas. Patients were randomly assigned to receive either DTIC 750 mg/m2 IV day 1 every 28 days (Arm A) or DTIC 200 mg/m2 IV days 1–5 every 28 days (Arm B). Pharmacokinetics were studied in 6 patients on each arm using HPLC analysis. Thirty-nine patients (30 male, 9 female), ages 27–67 years (median 53) were entered on the study (20 on Arm A, 19 on Arm B). No objective responses were seen. Median time to progression was 3 months. Median survival was 8 months. Treatment was generally well tolerated. Major toxicities were grade 1–2 nausea (33%), lethargy (28%), diarrhea (15%), alopecia (15%), and grade 3 neutropenia (8%). Four patients on Arm A had mild self-limited episodes of intravascular hemolysis occurring immediately after drug infusion, the mechanism of which is unknown. Mean AUC for DTIC, HMMTIC (5-[3-hydroxymethyl-3-methyl-1-triazeno] imidazole-4-carboxamide), and MTIC (5-[3-methyl-1-triazeno] imidazole-4-carboxamide), in Arm A were 14.8, 0.17, and 1.15 mM min, respectively. Corresponding values for Arm B (on day 1 of 5) were 1.7, 0.06, and 0.29 mM min, respectively. The predicted HMMTIC and MTIC exposure over 5 days for Arm B, based on the day 1 data, is higher than with Arm A. We conclude that DTIC is well tolerated but does not have activity in patients with recurrent gliomas. The 5-day schedule appears less toxic, and pharmacokinetic studies show that it provides greater exposure to MTIC and HMMTIC compared to the one-day schedule.
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  • 78
    ISSN: 1573-7373
    Keywords: astrocytomas ; chemotherapy ; drug resistance ; glioblastomas ; recurrence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Malignant gliomas are largely resistant to current chemotherapeutic strategies often displaying a multidrug-resistant phenotype. Mechanisms involved in drug resistance are reduced cellular drug accumulation through membrane efflux pumps, drug detoxification as well as alterations in drug target specificity. In 27 primary and 17 secondary glioblastomas and their astrocytic precursor tumors, we studied the immunohistochemical expression profile of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), metallothionein, and topoisomerase II α. Glial tumor cells in all glioblastomas showed constant up-regulation of LRP, MRP, and topoisomerase II α. P-gp was found in 90% of the primary and 60% of the secondary glioblastomas. In precursor tumors, these drug resistance-related factors were expressed in varying proportions. Metallothionein, also found in normal and activated astrocytes, was retained in all neoplastic phenotypes. Furthermore, metallothionein, P-gp, LRP, and topoisomerase II α were strongly expressed by normal and neoplastic vessels which may confer to impaired penetration of therapeutic agents through the blood–brain and blood–tumor barrier. However, the expression profiles of drug resistance-related proteins neither differed between primary and secondary glioblastomas nor revealed any correlation to precursor or recurrent tumors. Nevertheless, inhibition of these factors may be promising approaches to the management of malignant gliomas.
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  • 79
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    Pharmacy world & science 22 (2000), S. 31-32 
    ISSN: 1573-739X
    Keywords: Diuretics ; Drug therapy ; Elderly ; Evidence‐based ; Hypertension ; Ischaemic heart disease ; Quality of life ; Stroke ; Systematic review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Hypertension is very common, occurring in over 50% of older people, and is a major risk factor for stroke and ischaemic heart disease. Based on systematic reviews there is evidence to show that drug treatment of hypertension in older people saves lives and prevents unnecessary morbidity. There is also strong evidence to support the use of diuretics as first line agents. Quality of life does not appear to be reduced by antihypertensive drug therapy, although more high quality research is needed. Through the use of drug treatment older people with hypertension can continue to contribute to society and live active lives.
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  • 80
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    Veterinary research communications 24 (2000), S. 169-177 
    ISSN: 1573-7446
    Keywords: atovaquone ; azithromycin ; chemotherapy ; mouse ; Toxoplasma gondii
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mice were infected intraperitoneally with 10 000 tachyzoites of Toxoplasma gondii (RH) strain and, 24 h later, were treated orally for 10 days with atovaquone and azithromycin, either alone or in combination. Evaluation of the efficacy of the drugs was performed by microscopic examination of smears prepared from the organs of the mice, and by subinoculation of visceral and brain suspensions from surviving mice into healthy mice at the end of the experiments. It was found that 58%, 83% and 100% of the mice survived after administration of 75, 150 or 200 mg/kg per day of azithromycin, respectively. Moreover, 8%, 17% and 25% of the mice survived after treatment with atovaquone at 20, 50 or 100 mg/kg per day, respectively. No synergistic or additive effects of combinations of atovaquone and azithromycin were observed. However, azithromycin did not eradicate the parasite from the brain and viscera of the infected mice, whereas atovaquone at 20, 50 and 100 mg/kg per day removed the parasite from viscera and at 100 mg/kg per day eradicated the parasite from the brain of infected mice. The combinations of atovaquone and azithromycin failed to completely eradicate the parasite from the brain and viscera of infected mice.
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  • 81
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    Veterinary research communications 24 (2000), S. 245-260 
    ISSN: 1573-7446
    Keywords: anthelmintic ; antibiotic ; camel ; chemotherapy ; enzymes ; pharmacokinetics ; xenobiotic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent publications dealing mainly with the kinetics of antiparasitic and antibacterial agents, NSAIDs, and other drugs in camels are briefly reviewed. The kinetic data for most of these drugs indicated that they have longer absorption and elimination half-lives and slower systemic clearance in the camel compared to other animals. This corroborates earlier reports that suggested that the activities of drug-metabolizing enzymes and the capacity to biotransform and eliminate xenobiotics is lower in camels than in other ruminants. There is a clear need to establish basic kinetic data for the camel in order to avoid extrapolation of drug dosage regimens and withdrawal times from data for other animals, as this may result in irrational use of drugs in camels.
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  • 82
    ISSN: 1573-7373
    Keywords: recurrent choroid plexus papilloma ; chemotherapy ; CCNU ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A pregnant 33-year old woman developed nystagmus and cerebellar ataxia. A tumor in the roof of the fourth ventricle was diagnosed. The tumor was subtotally removed using microneurosurgical techniques. The histopathological diagnosis was choroid plexus papilloma (CPP). Twenty-one months later, the tumor recurred and was reoperated. Histologically the tumor displayed now increased mitotic activity and pleomorphism. Radiation therapy of the neuroaxis was performed. Within 59 months, the CPP recurred 3 more times with neuroradiological evidence of extensive spinal seeding. After several palliative irradiations, including 2 gamma-knife boosts, the patient was referred to chemotherapy. She was treated with CCNU (Lomustin) 100 mg/m2 orally (12 cycles, cumulative dosis 1440 mg/m2). Within 42 months, there was no new local recurrence and spinal seeding showed significant regression. Clinically the patient improved and stabilized, but needs continuous support because of persisting severe gait ataxia. The course of disease in our patient provides evidence for therapeutic efficacy of CCNU in recurrent CPP.
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  • 83
    ISSN: 1573-7373
    Keywords: glioma ; chemotherapy ; docetaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objective of the study was to assess the efficacy of docetaxel in recurrent supratentorial malignant gliomas. The sample size of the study was determined by the Gehan's method for a response rate of 20% and a β error of 5%. In the first step 14 patients (age 27–69, median 50; Karnofsky index 50–90, median 75) with recurrent malignant glioma after surgery, radiotherapy and nitrosourea, were enrolled (12 glioblastomas, 2 anaplastic astrocytomas). Docetaxel at the initial dose of 80 mg/m2 was administered every 3 weeks until progression or unacceptable toxicity. A total of 41 cycles was administered. Patients received a median of two cycles (range 1–6). No complete or partial response was observed. Therefore, according to the design of the study, no additional patients were enrolled and the trial was terminated. Two stabilizations were observed (14 and 15 weeks). Median TTP was 7 weeks (44 days). Median overall survival from recurrence was 26.5 weeks (6.4 months). Grade 3–4 neutropenia was observed in 8 patients (57%) but no life-threatening toxicity was observed. Other toxicities were uncommon and mild. Dose reduction was performed in 5 patients. This study suggests that docetaxel displayed no significant activity in patients with malignant recurrent gliomas.
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  • 84
    ISSN: 1573-7373
    Keywords: glioblastoma multiforme ; chemotherapy ; radiotherapy ; phase II trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent publications support the use of preradiation chemotherapy in the treatment of selected primary brain tumors. In the pediatric population, this treatment strategy often delays radiotherapy and may improve the outcome in patients. This manuscript describes the use of a preradiation chemotherapy approach for adult patients with newly diagnosed glioblastoma multiforme. The main objective of this trial was to determine the feasibility of delivering up to 3 monthly cycles of a 72 h continuous simultaneous intravenous infusion of BCNU (40 mg/m2/day) and cisplatin (40 mg/m2/day). Patients were evaluated for tumor response or progression after each cycle. Following the completion of the chemotherapy treatments or evidence of tumor progression, patients underwent external beam radiotherapy. A dose of 45 Gy was delivered to the pretreatment tumor volume plus surrounding edema and a margin of 3.0 cm. An additional 14.4 Gy was delivered to the preoperative volume plus a 2 cm margin. Fifty patients were enrolled, 47 were eligible and analyzable. Overall, 79% of patients were able to complete at least 2 cycles of treatment, exceeding the predefined measure of feasibility. One patient achieved a complete response, 10 patients a partial response and 18 patients had stable disease at completion of the chemotherapy treatments. Twenty-four patients experienced grade 4 toxicity, mostly hematologic. All patients were able to undergo radiotherapy following chemotherapy. These results indicate that a preradiation strategy is feasible. Although responses to the chemotherapy were seen, a phase III trial is needed to determine whether this approach provides an advantage over standard treatment; such a phase III trial has been undertaken by ECOG.
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  • 85
    ISSN: 1573-7373
    Keywords: chemotherapy ; estramustine ; estramustine-binding protein ; glioma ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Estramustine is a chemotherapeutic drug, used in the treatment of prostatic carcinoma. In the prostate, it binds specifically to a 46 kDa glycoprotein called estramustine-binding protein (EMBP), which consists of three polypeptide components; C1, C2, and C3, each coded for by a specific gene. Expression of EMBP and binding of estramustine has also been detected in malignant glioma in both rats and humans. Elevated levels of this protein in astrocytoma have proved to correlate with poor prognosis. In the present work, expression of all three polypeptide components of EMBP was confirmed in an orthotopic rat glioma model with nested reverse transcriptase PCR and Western blot (molecular weights of 8, 10, and 12 kDa). Specific binding of estramustine with a K d of 40 for male and 50 for female rats, and a total number of binding sites of 0.7 and 0.4 pmol/mg proteins for male and female rats respectively, was demonstrated with Scatchard plot analysis. These binding characteristics are similar to those of prostatic EMBP. Further studies to elucidate how EMBP expression affects the effect of estramustine treatment, and its putative prognostic value is of special clinical interest. The confirmation of BMBP expression in BT4C rat glioma demonstrates its suitability as a model system for such studies.
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  • 86
    ISSN: 1573-7373
    Keywords: glioma ; chemotherapy ; prognosis ; interferon-β ; MCNU
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Combined treatment with interferon-beta, MCNU (Ranimustine), and radiotherapy was assessed in patients with malignant glioma who had not received previous cytotoxic drug therapy. Forty-three patients up to 75 years old with histopathologically confirmed malignant glioma were studied. All patients had tumors measurable by neuroimaging, a Karnofsky performance score exceeding 40, and an expected survival exceeding 2 months. A response rate of 49% (21/45) was observed, including 6 complete remissions (14%) and 15 partial remissions (35%). Of the 43 patients who completed initial therapy, 19 were given sequential maintenance therapy. Survival time was much longer with than without maintenance therapy. Toxic side effects were moderate and did not substantially affect patients' general condition. We concluded that this combination therapy had a pronounced effect on untreated malignant glioma, particularly in patients whose initial therapy was followed up with maintenance therapy.
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  • 87
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    Tropical animal health and production 32 (2000), S. 361-374 
    ISSN: 1573-7438
    Keywords: cattle ; chemotherapy ; diminazene ; homidium ; Kenya ; oxytetracycline ; transhumance ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Information was collected on the use of veterinary drugs by Maasai pastoralists in an area of Kenya where tsetse flies and trypanosomosis occur. Three herds of cattle were followed for between 4 and 5 years and records were kept of every veterinary drug treatment given by the livestock owners. Almost all treatments were either with the trypanocides homidium or diminazene, or with oxytetracycline by intramuscular injection. The rate of trypanocide use varied between 0.66 and 1.56 treatments per animal per year, while oxytetracycline use was between 0.20 and 1.00 treatments per animal per year. Farmers were injecting these drugs in the absence of veterinary supervision, obtaining their supplies mainly from local village shops or informal traders. Underdosing with trypanocides appeared to be uncommon and the indications were that farmers generally gave the drugs at dosage rates above the recommended standard dose. Accurate information on the dose rates of oxytetracycline could not be obtained, but it was noted that in most cases farmers gave a single injection rather than a course of treatment. In a proportion of cases, trypanocides and antibiotics were mixed together before injection. The farmers administered the drugs when disease was recognized and were rarely using trypanocides as prophylactics. Although necessity forces the livestock owners to obtain and use these drugs without veterinary supervision, there are concerns with regard to the possibility of drug misuse and the development of drug resistance.
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  • 88
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    Journal of neuro-oncology 46 (2000), S. 97-103 
    ISSN: 1573-7373
    Keywords: boswellic acids ; glioma ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Conventional malignant glioma therapy (surgery, radiation therapy and chemotherapy) does not yield satisfying results. The prognosis of the glioma patient depends more on the histological grading of the tumor and patient's age than on the therapy. Especially the adjuvant chemotherapy failed to date to influence survival time in glioma patients significantly. To improve results in malignant glioma therapy additional therapeutic regimes are necessary. In an earlier study we were able to show a significant reduction on perifocal edema by an extract from gum resin (EGR) accompanied with a clinical improvement in patients with malignant glioma. Also a decrease of urinary LTE4-excretion as a metabolite of leukotriene synthesis in brain tumors was observed. Furthermore we had found a proliferation inhibiting activity of the extract form EGR, the boswellic acids in cell cultures. The purpose of this experimental study was to elucidate the effects of the boswellic acids, which are constituents of an extract from gum resin on tumor growth in vivo. Female wistar rats weighing 200–250 g were treated with the drug 14 days after inoculation of C6 tumor cells into their right caudate nucleus and randomization into 4 groups. The treatment groups received different dosages and were compared to a control group without any additional treatment. Survival time of the rats in the highest dosage group (3 × 240 mg/kg body weight) was more than twice as long as in the control group (P 〈 0.05). In a second experiment the inhibition of tumor cell proliferation was examined. The C6 tumor cells were implanted into the caudate nucleus. Drug treatment was started immediately after implantation and stopped after 14 days. The animals were sacrificed and the brains were examined microscopically. Comparing low and high dosage of EGR treatment a significant difference in tumor volume was detected (P 〈 0.05). The proportion of apoptotic tumor cells in animals with high dose treatment was significantly larger than in the low dose (treatment) group (P 〈 0.05). These data demonstrate an influence of EGR in rat glioma growth and might represent a new therapeutic option on glioma treatment in man in future. Further experimental work on human gliomas is needed to definitively answer this question.
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  • 89
    ISSN: 1573-7373
    Keywords: astrocytoma ; 201thallium SPECT ; MRI ; MR spectroscopy ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose To compare chemotherapy treatment monitoring in astrocytoma by 201thallium single photon emission computed tomography (SPECT) and photon magnetic resonance spectroscopy (1H-MRS) with magnetic resonance imaging (MRI), and to evaluate the influence of morphological tumor changes on cerebral 201thallium uptake and metabolic changes in 1H-MRS. Materials and methods Six patients with highly malignant astrocytomas were followed with quantitative 201thallium SPECT, MRI, and 1H-MRS during chemotherapy. Maximum follow-up included six examinations per patient by either method during 18 months. Criteria were set for: (1) regression (≥ 25% tumor reduction), (2) status quo (〈 25% reduction and 〈 25% increase), and (3) progression of disease (≥ 25% tumor increase). Results were compared with the clinical state of disease. Changes of tumor volume, contrast enhancement, necrosis, hemorrhage and edema on MRI were compared to changes in 201thallium uptake volumes and 1H-MRS metabolite ratios. Results Six patients were followed with a total of twenty-four examinations with 201thallium SPECT, MRI and 1H-MRS, respectively, between February 1997 and October 1998. Five patients developed clinical progression of disease, 4 out of 5 cases showed SPECT progression, 4 out of 5 cases MRI progression, and 1 out of 2 interpretable cases 1H-MRS progression at final assessment before clinical deterioration. During the phase of clinically stable disease; (A) the criterion for regression or status quo was met in 10 out of 13 assessments with SPECT, 11 out of 13 with MRI, and 8 out of 9 interpretable 1H-MRS; (B) the criterion for progression was met in 3 out of 13 with SPECT, 2 out of 13 with MRI, and 1 out of 9 interpretable 1H-MRS. The accuracy of SPECT, MRI, and 1H-MRS in identifying changes of tumor burden concordant with patients' clinical course was 78%, 83%, and 82%, respectively. SPECT regression was associated with MRI decrease of tumor size, contrast enhancement, edema and hemorrhage. SPECT progression was associated with MRI increase of the same parameters and the increase of necrosis. 1H-MRS regression was associated with decrease of edema. 1H-MRS progression was associated with increase of tumor size, hemorrhage, and increase or decrease of contrast enhancement. Conclusions Both 201thallium SPECT and 1H-MRS evaluation showed sensitivity for detection of astrocytoma progression. We did not find a higher accuracy of SPECT or MRS than of MRI in astrocytoma chemotherapy monitoring. Treatment induced MRI changes were associated with 201thallium uptake variations. 1H-MRS was difficult to apply for astrocytoma treatment monitoring. Improvements regarding size of measurement area such as multivoxel MRS and fat suppression pulses appeared desirable, and also the use of functional techniques with superior resolution such as dual isotope SPECT. However, our results suggest that 201thallium SPECT and 1H-MRS can provide additional information to MRI for chemotherapy efficacy evaluation in selected cases.
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  • 90
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    Journal of neuro-oncology 48 (2000), S. 249-250 
    ISSN: 1573-7373
    Keywords: anticonvulsant drugs ; chemotherapy ; gliomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The reduced bioavailability of chemotherapeutic agents is one of the reasons that explains the limited efficacy of adjuvant chemotherapy in high grade glioma patients. We report how even the results of high dose sequential chemotherapy can be influenced by antiepileptic drugs.
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  • 91
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    Springer
    Journal of neuro-oncology 49 (2000), S. 105-115 
    ISSN: 1573-7373
    Keywords: glioma ; MRP ; chemotherapy ; RT-PCR ; immunohistochemistry ; antisense oligonucleotide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Drug resistance is a major clinical problem in the chemotherapy of human gliomas. The multidrug resistance-associated protein (MRP), a membrane transporter related to non-P-glycoprotein multidrug resistance, is overexpressed in some drug-selected cancer cell lines. To investigate whether MRP is involved in the intrinsic drug resistance of human gliomas, surgical specimens of 20 gliomas (11 glioblastomas, 6 anaplastic astrocytomas, and 3 astrocytomas), 3 normal brain specimens, and 4 glioma cell lines (U87MG, U251MG, U373MG, and T98G) were analyzed. The expression of MRP was studied by RT-PCR and immunohistochemistry in the surgical specimens. The MRP expression levels in the cell lines were assessed by the quantitative RT-PCR and Western blot analyses. Sensitivity to adriamycin (ADM), etoposide (VP-16), cisplatin (CDDP), and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), were determined by MTT assay, and antisense treatment was evaluated in the cell lines. The expression of MRP was detected in 9 of 11 glioblastomas and 3 of 6 anaplastic astrocytomas. The quantitative analyses of the cell lines revealed that the MRP mRNA and protein levels were increased 4.5-fold in the T98G cells as compared to U87MG. T98G cells showed the highest resistance to all drugs. Western blot analysis revealed that treatment with the antisense oligonucleotide reduced the level of MRP expression to 25% of the sense oligonucleotide treatment in T98G cells. The sensitivity to ADM, VP-16 and CDDP was significantly increased in the antisense-treated cells as compared with the sense-treated cells. These results suggest that the MRP expression may be related to the intrinsic multidrug resistance in human gliomas.
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  • 92
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    Journal of neuro-oncology 49 (2000), S. 165-170 
    ISSN: 1573-7373
    Keywords: brain tumor ; chemotherapy ; hydroxyurea ; meningioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Meningiomas represent 18–20% of all intracranial tumors and have a 10-year recurrence rate of 20–50%, despite aggressive surgery and irradiation. In addition, many tumors are not amenable to surgery due to their deep location or proximity to delicate structures. Chemotherapy is being explored as another potential treatment option for unresectable or refractory meningiomas. Hydroxyurea is an agent that inhibits ribonucleotide reductase and can induce apoptosis in meningioma cell cultures and animal models. We have placed 17 patients with unresectable or residual meningioma on hydroxyurea chemotherapy (20 mg/kg/d orally). The mean age of our cohort was 57.2 years; 13 patients were female. Eleven patients had actively growing tumors or neurological progression at the onset of chemotherapy. Sixteen patients were evaluable for response. Fourteen of the 16 patients (88%) responded with stable disease ranging from 20 to 144+ weeks (median 80 weeks; 10 patients still accruing time). Three of the responders progressed after 20, 36, and 56 weeks, respectively. Two patients had progressive disease after 10 weeks. Toxicity was hematologic in most patients; leukopenia was most common. Nine patients (53%) required dosage reductions (250–500 mg/d) secondary to hematologic toxicity. Hydroxyurea appears to have modest activity against meningiomas and should be considered in patients with unresectable tumors or large residual tumors following surgical resection.
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  • 93
    ISSN: 1573-7373
    Keywords: accelerated radiation therapy ; ACNU ; Ara-C ; chemotherapy ; high-grade glioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose To evaluate activity and toxicity of simultaneous ACNU and Ara-C with concurrent accelerated hyperfractionated radiotherapy in the treatment of high-grade glioma. Patients and Methods Thirty patients aged 23–71 years (median 47.5), 16 patients with glioblastoma multiforme (GBM) and 14 patients with grade-III glioma, received 93 courses of ACNU/Ara-C (median 4 courses) at following dose levels (ACNU/Ara-C in mg/m2/day): 70/90 (11 courses), 75/100 (36 courses) and 90/120 (46 courses). ACNU was administered IV on day 1 of each cycle, Ara-C as a 2 h-intravenous infusion on days 1–3. Patients received concomitant radiation therapy with 2 daily fractions of 1.75 Gy up to 57 Gy (median). Results Median survival of all patients was 13 months, 11 months for GBM and 〉 28 months for grade-III glioma; 31% (9 patients) survived longer than 24 months. The percentage of grade IV hematological toxicity was dose-dependent: 33% at the 70/90 dose level, 40% at 75/100 and 58% at 90/120. Six patients required platelet transfusion, 1 patient red blood cells; no febrile neutropenia occurred. Among 18 patients evaluable for response, 3 (17%) showed PR, 8 (44%) NC and 7 (39%) PD at completion of chemoradiation. No acute or late neurological toxicity occurred in this study. Younger age (p = 0.0001) and grade-III histology (p = 0.0009) were important prognostic factors for prolonged survival. Conclusion This chemoradiation regimen is active in malignant gliomas and can be safely recommended at a dose level using 70 mg/m2 ACNU together with 90 mg/m2 Ara-C.
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  • 94
    ISSN: 1434-3932
    Keywords: Schlüsselwörter  Bauchaortenaneurysma ; Lebensqualität ; Endovaskuläre Therapie ; Keywords  Aortic aneurysm ; Quality of life ; Endovascular ; Conventional therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract   Patient satisfaction plays an increasing part in the analysis of the outcome of medical treatment. The aim of the study was to compare health-related quality of life in patients with abdominal aortic aneurysm after endovascular or conventional surgery. A total of 40 patients were included (20 treated by endovascular and 20 by conventional surgery). A questionnaire with 28 items similar to the SF-36 was answered during scheduled appointments. On the third postoperative day, the conventionally treated patients were more frequently confined to bed (80% vs. 32%) and complained of intervention-related pain (90% vs. 42%) and incisional pain (26% vs. 15%); 55% of the patients suffered from obstipation (vs. 5% of the endovascular group). Furthermore, the preoperative psychological stress seemed to be intensified. In comparable percentage, both the endovascular and conventionally treated patients were limited in social activities perioperatively. Sexual dysfunction was more frequent in the conventional group (33% vs. 13% three months postoperative). In addition, the conventionally treated patients were more limited in their physical activities (25% vs. 40%) and had more fear of ambulation (35% vs. 6%). The patients treated by an endovascular approach complained about frequent examinations (39% vs. 5%) that were often related to X-ray exposure (67% vs. 20%). All of the conventionally operated patients had a sense of improvement (vs. 89% of the endovascular group); nevertheless only 28% felt completely healthy, compared to 11% of the endovascular treated patients. Advantages of the endovascular treated patients were ”short hospital stay”, ”decreased pain”, ”smaller scars”, and a ”shorter confinement to bed”. After intervention the conventionally treated patients were more limited in almost all quality-of-life aspects. After 3 months, differences between the groups decreased except for sexual dysfunction and limited physical activities. The patients treated by endovascular surgery complained more about frequent X-ray examinations than the conventionally treated group.
    Notes: Zusammenfassung  Zur Bewertung eines Therapieerfolgs gewinnt der subjektive Aspekt der Patientenzufriedenheit zunehmend an Bedeutung. Ziel unserer Untersuchung war es, die medizinischen Aspekte der Lebensqualität vor, während und nach Behandlung eines infrarenalen Bauchaortenaneurysmas durch konventionelle oder endovaskuläre Operation zu vergleichen. Insgesamt 40 Patienten, 20 Patienten nach konventioneller und 20 Patienten nach endovaskulärer Bauchaortenaneurysmaausschaltung, die in unserer Klinik in dem Zeitraum 01.06.1997 bis 31.12.1998 operiert worden waren, erhielten einen in Anlehnung an den SF-36-Survey-Fragebogen entwickelten Fragenkatalog mit 28 Fragen über die perioperative Lebensqualität. Am 3. postoperativen Tag waren deutlich mehr konventionell operierte Patienten bettlägerig (80 vs. 32%), gaben stärkere Schmerzen (90 vs. 42%) sowie Narbenbeschwerden (26 vs. 15%) an und litten unter Verdauungsproblemen (55 vs. 5%). Sie waren außerdem vor der Operation durch den Eingriff psychisch belasteter als die Vergleichsgruppe. Die Patienten beider Gruppen fühlten sich perioperativ in einem vergleichbaren Prozentsatz in der Ausübung gesellschaftlicher Aktivitäten beeinträchtigt. In der konventionell operierten Patientengruppe waren postoperative Sexualfunktionsstörungen signifikant häufiger als bei den endovaskulären Patienten (33 vs. 13% 3 Monate postoperativ). Im postoperativen Intervall von 3 Monaten waren die konventionellen Patienten physisch weniger belastbar (25 vs. 40%) und hatten stärkere Angst, sich frei zu bewegen (35 vs. 6%); 39% der endovaskulären Patienten empfanden die postoperativen Kontrolluntersuchungen als belastend, 67% empfanden die Strahlenbelastung bei den Kontrollen als negativ (konventionell 5 bzw. 20%). Alle konventionell operierten Patienten hatten das Gefühl, dass das Bauchaortenaneurysma ausgeschaltet sei (endovaskulär 89%). Vollkommen gesund fühlten sich 3 Monate postoperativ lediglich 28% der konventionell operierten Patienten bzw. 11% der endovaskulären Patienten. Als größte Vorteile der endovaskulären Methode wurden ”kurzer Krankenhausaufenthalt”, ”wenig Schmerzen”, ”kleine Narbe” und ”kurze Bettlägerigkeit” genannt. Die konventionell therapierten Patienten sind in ihrer Lebensqualität perioperativ deutlich mehr beeinträchtigt als die endovaskulär behandelten. Nach 3 Monaten finden sich jedoch bis auf den Bereich der Sexualfunktionsstörungen, der physischen Belastbarkeit und der Bewegungsfreiheit keine signifikanten Unterschiede in beiden Kollektiven. Durch die regelmäßigen Nachuntersuchungen mit Strahlenexposition fühlen sich die endovaskulär behandelten Patienten stark belastet.
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  • 95
    ISSN: 1573-689X
    Keywords: bedside wellness system ; chemotherapy ; fatigue ; emesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The bedside wellness system (BSW) is effective for decreasing stress and improving mental well-being and should help relieve the side effects and mental disorders of patients during cancer chemotherapy. Methods: The study was a randomized clinical trial. After giving informed consent, patients were randomly assigned to the BSW intervention or control groups. The patients were given the Hospital Anxiety and Depression Scale (HADS) test before the trial to evaluate their emotional baseline. The Cancer Fatigue Scale, which was developed at our institute, and face visual analog scale were used to measure the emotional state and subjective feelings before and after the trial. The degree of emesis was measured using a visual analogue scale after the experience. We set up the system in a room in the outpatient clinic of the National Cancer Center New Hospital Building. Results: The decreases in the fatigue score and emesis score 3–5 days after chemotherapy were statistically significant (both p 〈 0.05) and carry-over effects were detected. Conclusions: BSW intervention therapy is an effective way to treat fatigue and emesis. This virtual reality system is a new therapeutic method that can be used in palliative medicine.
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  • 96
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    Cellular and molecular neurobiology 20 (2000), S. 217-230 
    ISSN: 1573-6830
    Keywords: arabinose ; mannitol ; blood–brain barrier ; brain ; drug ; chemotherapy ; osmosis ; shrinkage ; permeability ; tumor ; bulk flow ; tight junctions ; capillary
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Osmotic opening of the blood–brain barrier by intracarotid infusion of a hypertonic arabinose or mannitol solution is mediated by vasodilatation and shrinkage of cerebrovascular endothelial cells, with widening of the interendothelial tight junctions to an estimated radius of 200 Å. The effect may be facilitated by calcium-mediated contraction of the endothelial cytoskeleton. 2. The marked increase in apparent blood–brain barrier permeability to intravascular substances (10-fold for small molecules) following the osmotic procedure is due to both increased diffusion and bulk fluid flow across the tight junctions. The permeability effect is largely reversed within 10 min. 3. In experimental animals, the osmotic method has been used to grant wide access to the brain of water-soluble drugs, peptides, antibodies, boron compounds for neutron capture therapy, and viral vectors for gene therapy. The method also has been used together with anticancer drugs to treat patients with metastatic or primary brain tumors, with some success and minimal morbidity.
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  • 97
    ISSN: 1573-7217
    Keywords: cerbB2 ; chemotherapy ; neoadjuvant ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent advances in the detection and treatment of breast cancer have led to an intensive search for new markers of both prognosis and chemoresponsiveness. The oncogene cerbB2 has proved to be one of the most promising markers currently under study, both as a predictor of chemoresponsiveness and as a marker of poor prognosis. In addition the increasing use of neoadjuvant chemotherapy has led to the loss of standard prognostic criteria. In order to study the potential role of cerbB2 expression as an indicator of chemoendocrine resistance and poor prognosis, both before and after chemotherapy, we obtained tumour sections from 283 women enrolled onto a neoadjuvant trial. In this trial patients were randomised to receive either primary surgery followed by adjuvant chemoendocrine treatment or neoadjuvant chemoendocrine therapy followed by surgery. CerbB2 status was determined immunohistochemically on all of these patients. Thirty-eight percent of the tumours were cerbB2 positive. There was no significant difference in expression between the adjuvant (41%) and neoadjuvant arms (35%). CerbB2 positive patients were much more likely to have shown non-response to chemoendocrine therapy (p〈0.001) and had a worse DES (p〈0.05). The best prognosis was seen in cerbB2 negative patients receiving neoadjuvant chemoendocrine therapy who showed a significantly better DFS (p〈0.05), than the cerbB2 negative patients receiving adjuvant therapy.
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  • 98
    ISSN: 1573-7217
    Keywords: breast cancer ; locally advanced ; neoadjuvant ; chemotherapy ; paclitaxel ; cisplatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background.In an earlier study, we have demonstrated a high response rate in metastatic breast cancer using paclitaxel (P) and cisplatin (C). A phase II study using the same regimen (PC) has been conducted in locally advanced breast cancer (LABC). Methods.A total of 72 consecutive patients with non-inflammatory LABC (T2 ≥ 4 cm, T3 or T4, N0–N2, M0). Patients were scheduled to receive 3–4 cycles of the neoadjuvant PC (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2 on day 1) every 21 days. Patients were then subjected to surgery and subsequently received 6 cycles of FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) or 4 cycles of AC (doxorubicin 60 mg/m2, and cyclophosphamide 600 mg/m2). Patients then received radiation therapy, and those with hormone receptor positive tumors were given adjuvant tamoxifen intended for 5 years. Results.The median age was 39 years (range, 24–78). Clinically, 7%, 58%, and 35% of patients had T2 ≥ 4 cm, T3, and T4, respectively. Disease stage at diagnosis was IIB (33%), IIIA (27%), and IIIB (40%). Complete and partial clinical response to PC was demonstrated in 13 (18%), and 52 (72%) patients, respectively. Of those patients with evaluable pathologic response (68 patients), complete pathologic response (pCR) was achieved in 15 (22%) patients. At a median follow-up of 22 (± 3.5) months, 58 (81%) were alive with no recurrence, nine (12%) were alive with evidence of disease, and five (7%) were dead. None of the patients achieving pCR has developed any relapse. The median overall survival has not been reached for all 72 patients with a projected 3-year survival (± SE) of 90% (± 4%). The median progression-free survival (PFS) was 42.1 (± 4.8) months with a projected PFS of 74% ± 7% at 3-years (for 68 patients). Conclusions.PC regimen in LABC produced a high pCR. The contribution of the other added modalities to survival could not be assessed.
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  • 99
    ISSN: 1573-7217
    Keywords: adjuvant treatment ; breast cancer ; chemotherapy ; immunotherapy ; radiotherapy ; randomized trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract With a median follow-up of 14 years, the combination of polyadenylic–polyuridylic acid plus locoregional radiotherapy (257 patients) has significantly improved disease-free survival (p = 0.03) and significantly reduced the incidence of metastases (p = 0.04) when compared to CMF alone (260 patients), in women with operable breast cancer. The trial does not, however, permit an appreciation of the respective role of radiotherapy and PolyAU in these results.
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  • 100
    ISSN: 1573-7217
    Keywords: advanced breast cancer ; cyclophosphamide ; docetaxel ; epirubicin ; G-CSF ; second-line ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose.A phase II study was performed to investigate the efficacy and tolerance of alternating docetaxel and epirubicin/cyclophosphamide plus recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with advanced breast cancer who failed previous non-anthracycline/taxane-containing palliative chemotherapy. Patients and methods.Between November 96 and June 98, a total of 45 patients participated in this trial. Chemotherapy consisted of docetaxel 100 mg/m2 given as a 1-h infusion on day 1, and epirubicin 100 mg/m2 plus cyclophosphamide 800 mg/m2 both adminstered on day 21. G-CSF 5 μg/kg/day was given subcutaneously from days 22–28 during each cycle. Treatment courses were repeated every 42 days for a total of three courses unless prior evidence of progressive disease. Results.The overall response rate was 57.8% (95% confidence interval, 42.1–72.3%), including seven complete (15.5%) and 19 partial remissions (42.3%); nine patients (20%) had stabilization of disease and 10 (22.3%) progressed. The median time to treatment failure was 7.0 months (range 1.5–26.0), and the median overall survival time 15.0 months (range 2.0–37.0+) with 12 patients (27%) currently still alive with metastatic disease. Myelosuppression was commonly observed with WHO grade 3/4 neutropenia in 20 patients (44%) complicated by septicemia in five (11%). Severe nonhematologic toxicity included stomatitis in five patients (11%), skin and peripheral neurotoxicity each in one patient; alopecia was seen in all 45 patients with complete hair loss in 26 (58%). Conclusions.Our data suggest that alternating docetaxel and epirubicin/cyclo-phosphamide plus G-CSF is an effective and tolerable second-line combination regimen for the treatment of advanced breast cancer.
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