Biweekly docetaxel-irinotecan with filgrastim support in pretreated breast and non-small-cell lung cancer patients. A phase I study.

BACKGROUND: Docetaxel (DTX) has been shown to be a very active drug in both breast cancer (BC) and non-small-cell lung cancer (NSCLC). Irinotecan (CPT-11) is also active in NSCLC, and has shown promising antitumor activity in pretreated BC. PURPOSE. To define the MTDs of these two drugs given together every other week with the use of filgrastim support in pretreated BC and NSCLC patients. PATIENTS AND METHODS: Patients (aged 18-70 years, performance status < or =2) with advanced NSCLC or BC who had received at least one prior chemotherapy regimen were candidates for this phase I study. The starting DTX and CPT-11 doses were 60 mg/m(2) and 80 mg/m(2). Doses were alternately escalated at each step by 10 mg/m(2) for both drugs. Filgrastim 300 microg/day was given subcutaneously from days 4 through 7 of each cycle. RESULTS: From April 2000, 41 patients were included in the trial (27 BC, 14 NSCLC). All BC patients had received epirubicin plus paclitaxel (with or without cisplatin) as first-line treatment. Of the 14 NSCLC patients, 12 had received cisplatin-based first-line therapy, and 8 patients had been pretreated with paclitaxel. The dose escalation proceeded through five dose levels up to DTX and CPT-11 doses of 80 mg/m(2) and 100 mg/m(2), respectively. Overall, ten patients showed dose-limiting toxicity during the first cycle, diarrhea in seven and neutropenia in the remaining three. Considering all 218 cycles delivered, grade 3 or 4 neutropenia occurred in 14 patients (34%), with only one episode of neutropenic fever, while severe diarrhea was observed in 9 patients (23%). A total of 21 objective responses were registered (four complete) for an overall response rate of 51% [95% CI 35-67]. A major response was seen in 16 of the 27 BC patients (59%) and in 5 of the 14 NSCLC patients (36%). CONCLUSIONS: DTX and CPT-11 can be safely given together biweekly at adequate doses, with filgrastim support. In view of the promising activity data in both groups, phase II studies testing this combination in pretreated BC and NSCLC patients are ongoing.

Biweekly docetaxel-irinotecan treatment with filgrastim support is highly active in antracycline-Paclitaxel-refractory breast cancer patients.

PURPOSE: To evaluate the feasibility and activity of combination treatment with docetaxel (DTX) and irinotecan (CPT-11), given together every other week, combined with filgrastim support, in anthracycline- and paclitaxel-pretreated breast cancer (BC) patients. PATIENTS AND METHODS: Advanced BC patients pretreated with anthracycline- and paclitaxel-based chemotherapy were eligible. DTX (80 mg/m2) and CPT-11 (100 mg/m2) were given biweekly with filgrastim support (300 microg/day on days 4-7). RESULTS: Fifty patients (48 with metastatic and 2 with locally advanced cancer) were enrolled, with a total of 318 cycles being delivered. Thirty-one patients had visceral localizations. All patients had received epirubicin plus paclitaxel, with or without cisplatin, as front-line treatment for advanced disease. Overall, fatigue and diarrhea were the main chemotherapy-related toxicities in this study, being severe in 10 (20%) and 4 (8%) patients. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 18 (36%) and 6 (12%) patients, respectively. Red blood cell transfusions were required in 4 patients. A total of 32 objective responses were registered (overall response rate, ORR = 64%, 95% confidence interval = 49-77%), including 8 complete responses (16%). An additional 8 patients showed stable disease. After a median follow-up of 18 (range 4-29) months, 30 patients were still alive, and 19 were progression free; median progression-free and overall survivals were 10 and 23 months, respectively. CONCLUSIONS: Biweekly DTX/CPT-11 with G-CSF support is a well-tolerated and highly effective approach in anthracycline-/paclitaxel-pretreated patients. The very promising ORR and survival outcome observed in this subset of patients with a poor prognosis suggest that this regimen might play a major role in the management of this disease.