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  • 1
    ISSN: 1569-8041
    Keywords: metastatic breast cancer ; paclitaxel ; weekly 24-hour 5-FU/leucovorin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To evaluate the antitumor activity in terms of response rate (RR), time to progression (TTP) and survival of paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil (5-FU)/leucovorin in pretreated metastatic breast cancer (MBC). Patients and methods: Fifty-four patients with bidimensionally measureable disease were included during phase II. Thirty-two had anthracycline resistant disease. Treatment consisted of 5-FU (24-hour i.v. infusion) 2.0 g/m2, leucovorin (two-hour i.v. infusion prior to 5-FU) 500 mg/m2, weekly for six weeks (day 1, 8, 15, 22, 29, 36) and paclitaxel (three-hour i.v. infusion) 175 mg/m2 was administered additionally on days 1 and 22, q 50 days. Results: We observed complete remissions in 4% of patients (2 of 54), partial remissions in 55% (30 of 54), stable disease in 37% (20 of 54) and progressive disease in 4% (2 of 54). The overall RR was 59% (95% CI 48%–72%). The RR in 32 patients with anthracycline resistant disease was 59% (19 of 32). The median duration of response was 12 months (3–22), median TTP eight months (2–22) and median survival time 15 months (2–28). Neutropenia was common, but of CTC grade 2 or 3 in most patients. Nonhematologic toxicities mostly consisted of CTC grade 1 and 2 myalgia, diarrhea, mucosits, nausea and vomiting. Conclusions: Paclitaxel combined with weekly 24-hour infusional 5-FU/leucovorin is well tolerated in the second line treatment of MBC. High efficacy was documented even in the treatment of anthracycline resistant disease, which warrants further evaluation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: biochemical modulation ; 5-fluorouracil ; methotrexate ; pancreatic cancer ; phosphonacetyl-L-aspartate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To evaluate the effect of biochemical modulation by PALA and methotrexate on the therapeutic activity of 5-fluorouracil (5-FU) in patients with advanced pancreatic adenocarcinoma. Patients and methods: The treatment protocol consisted of phosphonacetyl-L-aspartate (PALA) 250 mg/m2 i.v. 15-minute infusion followed by methotrexate 200 mg/m2 i.v. 30-minute infusion on day 1 and 5-FU 600 mg/m2 i.v. push on day 2. Folinic acid was given at 15 mg/m2 p.o. every six hours for eight doses, starting 24 hours after methotrexate infusion. Cycles were repeated every two weeks. Results: Thirty patients with advanced chemotherapy-naive pancreatic cancer were included; 26 had measurable disease. Median age 56 years (27–72); median PS 1 (0–2). One PR (3.9%) was achieved; nine patients had stable disease. Median time to progression was 91 days. Median survival was 177 days and one year survival was 13.3% (4 of 30 patients). Treatment was well tolerated; diarrhea WHO grade 2 or 3 occurred in six patients; stomatitis WHO grade 2 and 3 in nine patients. Conclusions: Modulation of 5-FU by PALA and MTX given in this dose and schedule appears to be ineffective in patients with advanced pancreatic adenocarcinoma.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1335
    Keywords: Key words Bendamustine ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A phase II pilot study of bendamustine as salvage treatment in patients with advanced breast cancer was performed to determine the objective response rates and make further observations on the toxicity of this drug. A group of 37 patients, pretreated with chemotherapy for advanced disease, entered the trial. Treatment consisted of 150 mg/m2 bendamustine on days 1 and 2 of a 4-week treatment course. Patients continued to receive treatment until complete remission and then two further courses, until tumour progression or unacceptable toxicity ensued. A total of 36 patients received at least one treatment course and were assessable for toxicity; 33 patients were evaluable for treatment results. Dose-limiting grade 3 and 4 WHO toxicity occurred in 5 and 3 patients respectively; 27% of patients entered complete or partial tumour remission. The median time to tumour progression was 2 months with a range of 1–14 months. The efficacy of bendamustine was apparently independent of pretreatment with anthracyclines, suggesting a lack of cross-resistance between bendamustine and anthracyclines. It can be concluded that bendamustine in the dose and application schedule used here is active in the salvage therapy of women with advanced breast cancer. The toxicity was acceptable. Future studies have to confirm the data of this pilot trial and to define the role of bendamustine in the combination chemotherapy of metastatic breast cancer that has been suggested by previous trials.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 62 (1984), S. 203-212 
    ISSN: 1432-1440
    Keywords: Tumor heterogeneity ; ‘Short-term assays’ ; DNA damage ; Human tumor-stem cell assay ; Xenograft model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The evolution of medical oncology so far owes much to the preclinical and clinical development of antineoplastic agents. Prognostic factors and empiric treatment strategies have guided the clinician in his choice of drugs. In the light of increasing ethical restrictions met with phase I–II clinical trials and major advances in propagating human tumor cells outside the donor patient, a reappraisal of predictive tests in cancer chemotherapy is warranted. Among ‘short-term assays’ only the determination of steroid-hormone receptor content in tumor tissues has gained clinical acceptance, whereas other methods still suffer from theoretical or practical shortcomings. Both the human tumor stem cell assay and the xenograft model have revealed unique patterns of sensitivity for each individual tumor line. While interindividual heterogeneity among tumors sharing a common site of origin justifies efforts to develop predictive tests, microheterogeneity among tumor samples from the same donor patient limits the potential of this approach. Predictive tests should be performed in conjunction with clinical trials to ensure optimal extraction of information. As additional prognostic factors, they should in the near future accelerate drug development and reduce the hazard of unnecessary drug toxicity without therapeutic benefit.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Keywords: Small-cell lung cancer ; Primary resistance ; Relapse ; Vindesine ; Cisplatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty-eight pretreated patients with primarily resistant [6] or relapsed [32] small-cell lung cancer were treated with a combination of vindesine (3–4 mg/m2) and cisplatin (60–100 mg/m2). Eight patients responded to this therapy with three (8%) complete and five (13%) partial remissions. Minor responses were noted in 12 (32%) additional patients. Chemotherapeutic response was rare in regions of prior irradiation. In the complete remission group survival from start of vindesine/cisplatin therapy lasted 61, 48 and 38 weeks, respectively. In the “less-than-complete-remission” group median survival was 12 weeks. Nausea and vomiting were the prominent side-effects, while only mild to moderate myelosuppression was noticed in most cases. The vindesine/cisplatin combination showed significant activity in heavily pretreated small-cell lung carcinoma. However, the remission rates remain low in this unfavourable condition, which might be due to pronounced chemotherapeutic resistance in previously irradiated areas.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 5 (1999), S. 47-54 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die zytostatische Chemotherapie ist etablierter Bestandteil im Behandlungskonzept des kolorektalen Karzinoms. Im metastasierten Stadium führt eine auf 5-Fluorouracil-basierende Chemotherapie zu einer signifikant längeren Überlebenszeit und zu einer deutlichen Reduktion tumorbedingter Symptome. In den letzten Jahren wurden zudem mehrere Substanzklassen, die eine relevante Aktivität beim kolorektalen Karzinom zu besitzen scheinen und damit potentiell das therapeutische Arsenal erheblich erweitern könnten, entwickelt und klinisch geprüft. Im folgenden Artikel wird ein Überblick über den derzeitgen Entwicklungsstand der wichtigsten neuen Substanzen für die Therapie des kolorektalen Karzinoms gegeben.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 49 (1984), S. 471-472 
    ISSN: 1432-0584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 105 (1983), S. 162-165 
    ISSN: 1432-1335
    Keywords: Aclacinomycin A ; Phase II study ; Refractory neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Aclacinomycin A (ACM) is a new anthracycline antibiotic with a reduced cardiac toxicity in animal models. A phase II study was performed in a total of 25 patients, 23 of whom are evaluable for response. All suffered from recurrent and advanced tumors. Pretreatment consisted of at least four different chemotherapeutic agents (range: 4–9). Lung cancer patients (3/9) were irradiated to the mediastinum. Eighteen patients were pretreated with doxo- or daunomycin. The dose for solid tumors was 2–3 mg/kg given on 3 consecutive days every 3 weeks. Leukemia patients received a daily dose of 20 mg/m2, and standard response criteria were used. Marked reductions of leukocyte counts were achieved in leukemia patients. The overall response rate was about 15% in solid tumors, but major objective responses (CR+PR) have not been observed. Myelosuppression was commonly moderate in solid tumor patients, nausea and vomiting were rare, and alopecia was not induced. Cumulative cardiotoxicity was not evaluated in this trial. Treatment with ACM requires further investigation in acute leukemias and solid tumors, not pretreated with anthracycline antibiotics.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1440
    Keywords: Small cell bronchogenic carcinoma ; Induction therapy ; Maintenance ; Remission rate ; Survival ; Kleinzelliges Bronchialkarzinom ; Induktionsbehandlung ; Erhaltungstherapie ; Remissionsraten ; Überlebenszeiten
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Seit Juli 1978 wurden 103 Patienten mit inoperablem kleinzelligem Bronchialkarzinom mit der Zytostatikakombination Adriamycin, Cyclophosphamid und Vincristin (ACO) behandelt. Im Stadium „limited disease“ (n=64) erfolgte während des zweiten Chemotherapiekurses eine prophylaktische Schädelbestrahlung, nach dem vierten eine konsolidierende thorakale Bestrahlung. Nach Erreichen einer kompletten Remission erhielten die Patienten prospektiv randomisiert Etoposid oder keine weitere spezifische Therapie. Ein objektives Ansprechen konnte bei 88/100 auswertbaren Patienten erzielt werden. Im Stadium „limited disease“ fanden sich 72%, im Stadium „extensive disease“ nur 33% komplette Remissionen. Im Stadium „limited disease“ betrug die hochgerechnete mediane Überlebenszeit 15,8, im Stadium „extensive disease“ 9,3 Monate (p〈0.005). Es leben noch 29 Patienten, 4 rezidivfrei länger als 24 Monate. Patienten mit kompletter Remission hatten eine statistisch signifikant (p〈0.001) längere Überlebenszeit als Patienten mit geringerem Ansprechen. Regelmäßig traten gastrointestinale und hämatologische Nebenwirkungen auf, drei Patienten starben während der Induktionsphase an Infektionen. Die kurzzeitige Induktionsbehandlung verbesserte jedoch den Krankheitsverlauf subjektiv und objektiv. Bisher ist kein positiver Effekt der zyklischen Etoposid-Gabe nach ACO festzustellen.
    Notes: Summary Since July 1978 one hundred and three consecutive patients with unresectable small cell bronchogenic carcinoma were treated with a combination of doxorubicin, cyclophosphamide and vincristine (ACO). In limited disease patients (64) the second chemotherapy course was followed by prophylactic cranial irradiation, the fourth by irradiation towards primary disease sites. Complete responders were randomised to either receive etoposide or no further maintenance therapy. Objective responses were reached in 88/100 evaluable patients, with 72% of complete remissions in limited-stage disease and 33% in extensive disease, respectively. The actuarial median survival time for limited disease patients was 15.8 months compared to 9.3 months in extensive disease (p〈0.005). 29 of the 100 patients remain still alive, 4 for more than 24 months without disease recurrence. The survival advantage of patients reaching complete remissions relative to those who did not is highly significant (p〈0.001). Acute gastrointestinal and hematological side effects were common, with possibly three drug-related deaths from infections during transient granulocytopenia (mean nadir: 600–900 cells/mm3). The present induction regimen using only four courses of chemotherapy produces high complete remission rates on roentgenography and bronchoscopy and improved survival in the majority of patients. Thus far any effectiveness of etoposide-maintenance therapy following ACO could not be substantiated.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1440
    Keywords: Testicular neoplasms ; Stage II ; Combination chemotherapy ; Radiotherapy ; Lymph node dissection ; Testikuläre Tumoren ; Stadium II ; Kombinierte Chemotherapie ; Radiotherapie ; Lymphknoten-Exstirpation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Seit 1975 wurden 140 Patienten mit retroperitoneal-metastasierten nicht-seminomatösen Hodentumoren nach Orchiektomie und retroperitonealer Lymphadenektomie sequentiell alternierend mit den Zytostatika-Kombinationen Velbe/Bleomycin und Adriamycin/Cisplatin plus/minus Radiotherapie behandelt. Davon erhielten 68 Patienten nach totaler retroperitonealer Lymphadenektomie mit postoperativ normalisierten Tumormarkern (Stadium IIA) 6 Chemotherapie-Kurse, woran sich bei 35 Patienten eine Strahlentherapie anschloß. Vierzig Patienten wurden nach subtotaler retroperitonealer Lymphadenektomie oder bei postoperativ erhöhten Tumormarkern (Stadium IIB) und 32 Patienten nach palliativer Lymphadenektomie (Stadium IIC) mit mindestens 12 Chemotherapie-Kursen und fakultativer intermittierender Radiotherapie und/oder Relaparotomie behandelt. Der Vergleich der Behandlungsergebnisse bei den Stadien IIA und IIB ergab unabhängig von der zusätzlichen Radiotherapie nach der „Life-table“-Methode Vier-Jahres-Überlebensraten zwischen 80 und 100%. Diese günstigen Resultate sind mit den Ergebnissen bei 34 nicht adjuvant behandelten Patienten ohne histologisch nachweisbare retroperitoneale Metastasierung (Stadium I) vergleichbar. Ausdruck einer statistisch signifikant schlechteren Prognose bei fortgeschrittener retroperitonealer Metastasierung ist eine Vier-Jahres-Überlebensrate von 12% bei den Patienten im Stadium IIC.
    Notes: Summary Following orchiectomy and retroperitoneal lymph node dissection (RND) 140 patients with stage II non-seminomatous testicular cancer were treated by sequential combination chemotherapy consisting of vinblastine/bleomycin and adriamycin/cis-dichlorodiammineplatinum(II) (DDP), plus/minus radiotherapy. 68 stage IIA-patients (complete RND and normal tumor-markers thereafter) received 6 courses of chemotherapy, followed by radiotherapy in 35 patients. 40 stage IIB-patients (minor residual disease after RND or elevated tumor-markers after RND) and 32 stage IIC-patients (advanced residual disease after RND) were treated by at least 12 chemotherapy courses and optional intermittent radiotherapy and/or relaparotomy. In stage IIA and IIB disease the actuarial 4-year survival rates were between 80 and 100%. These favourable results were not significantly influenced by additional radiotherapy and corresponded to the survival rates for 34 stage I-patients. For stage IIC-patients the prognosis was significantly worse with a 12% 4-year survival rate.
    Type of Medium: Electronic Resource
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