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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Annals of surgical oncology 2 (1995), S. 26-31 
    ISSN: 1534-4681
    Keywords: Sarcoma ; Gastrointestinal tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Primary gastrointestinal sarcomas are uncommon, and the clinicopathological determinants of survival remain unclear. In order to correlate clinical presentation, pathological assessment, and treatment with outcome, we have analyzed our institution's recent experience with these tumors. Methods: Records of adult patients admitted to our institution between July 1982 and December 1991 were reviewed. Results: During this period, 38 adult patients (〉16 years of age) were admitted to our institution with a primary gastrointestinal sarcoma. They accounted for 2% of all adult sarcoma admissions during that period. The study population was composed of 26 men and 12 women. Ages ranged from 29 to 82 years (mean 59). Disease was localized to the primary site in 30 patients (81%). The stomach was the most frequent site of disease (20 cases). The small bowel was affected in nine cases (five duodenum, four jejunum) and the large bowel in nine cases (two colon, seven rectum). Ninety-two percent of patients were symptomatic at presentation. A complete resection was performed in 27 cases, incomplete resection in seven cases, and biopsy only in the remaining three patients. Nine patients received doxorubicin-based chemotherapy. Leiomyosarcoma (n=35) was the predominant histological diagnosis. Twenty-six tumors were classified as high grade (68%) and 12 as low grade (32%). Overall actuarial 5-year survival was 28% (median follow-up 26 months). Weight loss (p=0.02) and pain at presentation (p=0.05) were adverse prognostic factors. Histological grade (p=0.0002), completeness/extent of surgical resection (p=0.005), or a small bowel primary site were significant determinants of overall survival. The resection of contiguous organs did not affect survival if the primary tumor was completely excised (p=0.422). Age, race, sex, presentation (prior surgery), tumor size, or adjuvant therapy were not significant prognostic factors. Recurrence was noted in 44% after complete resection, and mean time to recurrence was 9 months (median 7, range 〈1–37). Hepatic metastases (42%) and local recurrence (42%) were the predominant sites of initial failure. For patients with a complete resection, grade was the major prognostic determinant (5-year survival: high grade/complete resection 18% vs. low grade/complete resection 72%, p=0.002). Conclusion: The prognosis of gastrointestinal sarcomas is poor. Complete surgical excision is the optimal therapy. However, our results suggest that surgery alone is inadequate for high-grade tumors. We believe that these patients should be considered candidates for investigational adjuvant therapies.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1534-4681
    Keywords: Blood ; Transfusion ; Recurrence ; Sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Allogeneic blood transfusion (BT) has been implicated as an unfavorable factor influencing cancer recurrence and overall survival. Methods: To investigate this, 232 consecutive localized, high-grade extremity soft tissue sarcoma (STS) patients admitted between January 1, 1983, and December 31, 1989, were analyzed from our prospective database by univariable and Cox multivariable statistical methods. Results: Twenty-eight patients developed a local recurrence (LR). Factors found significantly unfavorable for the rate of developing an LR by uni- and multivariable tests were age 〉60 years and positive microscopic margin. Eighty-nine patients developed a distant metastasis (DM) and 72 patients died of their tumor. Median follow-up of survivors was 48 months. Unfavorable factors for DM and tumor mortality (TM) by univariable analysis included large size, deep tumor (that involved or was below the superficial fascia), positive microscopic margin, invasion of a vital structure, operative blood loss, duration of operation, and perioperative BT (whole blood or packed cells -24 to +48 h of curative operation). Multivariable analysis found large size, deep tumor, and positive margin significant independent unfavorable factors for DM and TM. The effect of BT was not a significant independent prognosticator for LR, DM, or TM by multivariable analysis (p=0.26, 0.56, 0.08, respectively), The only factor that was found to be significant in a multivariable analysis of factors contributing to postmetastasis survival was time 〈6 months until metastasis (p=0.008). BT had no significant impact on postmetastasis survival (p=0.42). There was a significant association between BT and deep, large tumors. As the size of deep tumors increased from 〈5, ≥5〈10, ≥10〈15, or≥15 cm, the amount transfused was 15, 16, 49, and 68% (p〈0.00001). Also, BT was significantly (p〈0.005) associated with low hematocrit at initial diagnosis, blood loss during surgery, and the length of the surgical procedure. Conclusions: These data emphasize the importance of size, depth, and margin on distant recurrence and death for localized high-grade extremity STS. In the absence of a randomized trial, the impact of allogeneic blood transfusion would appear to be due to its strong association with large size and deep tumor invasion. This study also highlights the importance of a multivariable analysis and long-term follow-up to better define this controversial question.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A total of 21 patients with advanced soft tissue sarcoma enrolled in a phase II trial of 3.5 g/m2 N-phosphonacetyl-l-aspartate (PALA) given intravenously every 3 weeks plus 50 mg/m2 dipyridamole (Persantine) given orally every 6 h. Dipyridamole administration was initiated 1 week before the first dose of PALA. Peak and trough plasma concentrations of dipyridamole were measured before and after the first dose of PALA in 14 patients. In all, 19 patients were evaluable for therapeutic response. One subject experienced partial regression of a pulmonary metastasis; no other major response was observed. Diarrhea was the most prominent toxicity; in one patient it was life-threatening and was associated with a severe rash. On the day preceding PALA administration, the median peak plasma concentration of dipyridamole was 2,208 ng/ml and the median trough value was 904 ng/ml. Similar values were obtained on the day of PALA administration. Although the levels achieved were similar to those required to modulate the activity of PALA in preclinical systems, the therapeutic results obtained in the present study were not superior to those reported for PALA alone in previously treated patients with soft-tissue sarcoma.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 15 (1985), S. 233-235 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary F-Ara-AMP (fludarabine phosphate) is an adenosine analogue that is resistant to deamination; it is a more potent cytotoxic compound than ara-A in experimental tumor systems. F-Ara-AMP was given by continuous IV infusion over 5 days once every 4 weeks to 27 evaluable adult patients with advanced cancer. The median Karnofsky performance status was 70% (range 50%–90%), and the median age was 58 years (range 41–74). In addition to adequate blood counts, a creatinine clearance of at least 60 ml/min was required. The initial dose level was 35 mg/m2/day. Dose-limiting myelosuppression was seen in the first patient. Subsequent patients were treated at lower doses. Myelosuppression was the only major toxicity. Leukopenia was generally more prominent than thrombocytopenia, but 2 patients experienced prolonged thrombocytopenia which prevented further therapy. Nausea was minimal, and neither renal nor neurologic toxicity was encountered. In patients with good renal function a dose of 25 mg/m2/day can be safely administered. However, because of apparent cumulative myelosuppressive effects a lower dose is more appropriate for patients who have had extensive prior chemotherapy or radiotherapy.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-0646
    Keywords: phase II ; fazarabine ; adenocarcinoma ; pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We conducted a phase II evaluation of fazarabine 1.75–2.0 mg/m2hr over 72 hours every 28 days in 14 previously untreated patients with advanced adenocarcinoma of the pancreas. The intial dose was 1.75 mg/m2/hr in 10 patients, and 2.0 mg/m2hr in 4 patients. The dose was escalated in 8 patients, including all 4 who started at the higher dose level. Toxicity was unexpectedly mild. The median WBC nadir was 4.4 (range: 2.4–15.8)×103/μl, the median absolute neutrophil nadir was 3.2 (range: 0.9–13.0)×103/μl, and the median platelet count was 134.0 (range: 48.0–291.0)×103/μl. Gastrointestinal toxicity was generally mild. No major responses were seen, excluding, with 95% confidence, a response rate in excess of 20%.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-0646
    Keywords: TomudexTM ; thymidylate synthase inhibitor ; pancreatic carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Background Currently available therapies for advanced pancreatic cancer offer only palliative benefits, and patients with this disease have a poor prognosis. We undertook a phase II trial of ZD1694 (TomudexTM), a quinazoline folate analogue that is a potent and selective thymidylate synthase inhibitor, to determine this analogue's efficacy and safety in patients with advanced pancreatic adenocarcinoma. Patients and methods ZD1694, 3.0 mg/m2, was administered to 42 adult patients with pancreatic adenocarcinoma as a 15-minute intravenous infusion every 3 weeks for up to 6 doses. Objective tumor response was assessed every 6 weeks; clinical examinations, adverse event assessments, and clinical laboratory tests were performed every 3 weeks. Results ZD1694 produced an overall response rate of 5% (95% confidence limits [CI], 1% to 16%) in the study group. Of 42 patients, 2 (5%) had a partial response, 12 (29%) had stable disease, 21 (50%) had disease progression, and 5 (11%) could not be evaluated for response. Grade 3 vomiting, grades 3 and 4 fever, grade 3 leukopenia, grade 4 thrombocytopenia, and grades 3 and 4 liver function elevations were reported. Toxic effects with ZD1694 were reversible and manageable. Conclusions ZD1694 has an acceptable safety profile but limited activity in patients with advanced pancreatic cancer.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-0646
    Keywords: doxorubicin ; iproplatin ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Forty-eight patients with advanced breast cancer were treated in a disease-specific phase I trial of doxorubicin and iproplatin combination chemotherapy. The doses of doxorubicin ranged between 30 and 50 mg/m2, and the doses of iproplatin ranged between 150 and 250 mg/m2. Myelosuppression was observed at all levels, but was dose-limiting at the highest level. In addition, nausea, diarrhea and malaise were prominent toxicities. Neither cardiac nor renal toxicity was encountered. Nine of 26 (35%) of previously untreated patients, and 5 of 22 (23%) previously treated patients demonstrated partial or complete responses. Although this combination possesses therapeutic activity, given its toxicities, further evaluation of doxorubicin in combination with iproplatin is not recommended.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 10 (1992), S. 313-316 
    ISSN: 1573-0646
    Keywords: phase II ; edatrexate ; adenocarcinoma ; pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We conducted a phase II evaluation of edatrexate in 17 previously untreated patients with advanced adenocarcinoma of the pancreas; 14 patients had at least one month of therapy. The initial dose was 80 mg/m2iv. Treatment was administered weekly for 5 weeks, then every other week. Toxicity was generally mild. The median WBC nadir was 5.4 (range 0.6–7.4)×103/μl, and the median platelet nadir was 164.0 (range 62.0–341.0)×103/μl. One patient died with sepsis and gastrointestinal bleeding associated with pancytopenia. Five patients had a mild rash. Nausea occurred in 6 patients, including 3 who had vomiting. In addition, 11 patients complained of vague malaise which seemed to begin within 24–48 hours after administration of edatrexate, and lasted for 2 to 3 days, resolving within 6 days of drug administration. Median survival was 85 days. Although 5 patients had stable disease, including one with relief of pain, no major responses were seen, excluding, with 95% confidence, a response rate in excess of 20%.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-0646
    Keywords: breast cancer ; Iproplatin ; CHIP ; phase II study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-five women with advanced breast cancer were treated in a phase II trial of iproplatin 275 mg/m2 administered intravenously every 4 weeks. All patients had measurable or evaluable indicator lesions, and had undergone treatment with no more than one previous chemotherapy regimen, including adjuvant chemotherapy. Two of the twenty-four evaluable patients (8%) experienced major therapeutic responses. One patient had a complete regression of pulmonary nodules lasting 18 + months; another had a partial regression of metastatic disease in the liver (4 months). The inevaluable patient was ineligible for the study because of previous radiation to the indicator lesions on her chest wall; nonetheless, she experienced a 10 month partial regression of those nodules. Myelosuppression was generally dose limiting; thrombocytopenia was more profound, but leukopenia was more prolonged. Nausea, vomiting, diarrhea, and general malaise were prominent toxicities, and led to discontinuation of therapy in 4 patients. Iproplatin has limited activity in previously treated women with advanced breast cancer.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 8 (1990), S. 187-190 
    ISSN: 1573-0646
    Keywords: carboplatin ; melanoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We report the results of a phase II evaluation of carboplatin (CBDCA) in 45 patients with advanced malignant melanoma. Of the 43 evaluable patients, 6 had been treated previously with chemotherapy; 11 had been treated with immunotherapy. The initial dose was 400 mg/m2 i.v. every 4 weeks; the dose was modified as required to achieve moderate myelosuppression. There was one complete response (duration 16 months) and six partial responses, for a major objective response rate of 16%. Toxicity consisted primarily of acute nausea and vomiting, and thrombocytopenia. The activity of CBDCA in this disease is similar to that of cisplatin and dacarbazine.
    Type of Medium: Electronic Resource
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