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Aims: To assess the maximum tolerability of a combined therapy regimen of gemcitabine and docetaxel, and to evaluate tumour response rate, survival time and tolerability in patients receiving these agents for advanced pancreatic carcinoma., Patients and Methods: Patients (n=68) with pancreatic carcinoma (advanced and/or unresectable tumour growth or histopathologically diagnosed metastases) were enrolled in a multicenter phase-I (n=25) and phase-II study (n=43). Treatment during phase II of the study was continued until either complete tumour remission (CR), tumour progression, indicated clinically or by means of radiological imaging, or until unacceptable toxicity occurred., Results: Phase I: the tolerability maximum of the combined agents was established at gemcitabine 1000 mg/m(2) and docetaxel 35 mg/m(2) with tolerable adverse events. Phase II: a total of 139 chemotherapy cycles were completed (mean, 3.2; range, 1-10). While CR was achieved in three of 43 patients (7%), in five further cases, partial remission (PR) was documented, amounting to an overall response rate (OR) of 18.6%. Eighteen patients showed stable disease (41.9%), whereas in 17 of 43 subjects (39.5%), primary tumour progression was detected. The median survival time was 9.0 months; the 1-year survival rate was 13.9% (six of 43 patients). These results were associated with a side-effect profile of moderate severity and acceptable quality of life (QOL)., Conclusion: The combination of gemcitabine and docetaxel for chemotherapy in unresectable pancreatic carcinoma was well tolerated. Survival time and 1-year survival rate proved promising and the regimen appears suitable for further evaluation in a prospective phase-III study setting.

Background: Poor treatment results obtained with palliative chemotherapy for advanced gastric cancer indicate the need for new effective and well-tolerated regimens., Patients and Methods: Forty-three patients with locally advanced or metastatic gastric cancer were enrolled in a phase II study to evaluate the efficacy and safety of combination chemotherapy with doxetacel 75 mg/m2 and cisplatin 75 mg/m2 given every three weeks., Results: Thirty-nine patients were evaluable for response. Four achieved a complete response and twelve a partial response, for an overall response rate of 37.2% (16 of 43 patients; 95% confidence interval (CI): 22.98-53.72). Median time to progression was 6.1 months and median overall survival 10.4 months. Forty-two percent of all patients were still alive at one year and twelve percent at two years. The major toxicity was leukopenia which reached grade 3-4 in 18.6% (n = 8) of the patients. However, no febrile neutropenia occurred. Non-haematological toxicities were usually mild to moderate. Grade 3 toxicities included diarrhea (9% of the patients), nausea and vomiting (7%), and alopecia (7%). Severe ototoxicity with or without peripheral neuropathy developed after completion of chemotherapy in two patients., Conclusions: These results suggest that the combination of docetaxel and cisplatin has moderate toxicity and is an effective regimen for the treatment of advanced gastric cancer, both with regard to response rate and survival.

Objective: A previous phase I trial in 14 pretreated patients with progressive advanced colorectal cancer demonstrated 750 mg/m2 to be the maximum tolerable dose of 5-fluorouracil (5-FU) administered as a five-day continuous infusion modulated by short infusions of 100 mg/m2 folinic acid twice daily. The dose-limiting toxicities were hand-foot syndrome and severe mucositis. A response rate of 21% and 50% stable disease could be achieved. In order to determine the effectiveness and tolerability, we initiated a multicenter phase II trial applying a 650 mg/m2 recommended dose of 5-FU and 100 mg/m2 folinic acid twice daily every three weeks., Patients and Methods: From January 1994 to July 1996, 88 advanced and progressive colorectal cancer patients either previously treated with a bolus schedule of 5-FU and folinic acid (34 patients) or without (54 patients) previous chemotherapy were included in this trial., Results: In the group of previously treated patients, therapy led to 6% (2 of 34 patients) remissions while stable disease could be observed in 68% (23 of 34 patients) of the patients. The median survival time was 14 months. The main toxicity was mucositis grade 3 in 15% of the previously treated patients and 10% in the nonpretreated patients. In the population of nonpretreated patients, the overall response rate was 15% (eight of 54 patients) and stable disease could be induced in 67% (36 of 54 patients). The median survival time was 13.7 months., Conclusion: This regimen is an active second-line therapy in advanced colorectal cancer with minimal toxicity, thus preserving the quality of life during palliative chemotherapy. Antitumor activity in previously untreated patients does not seem superior to that obtained with weekly regimens applying 24- or 48-hour continuous infusions of 5-FU and folinic acid.