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 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/m² and 80 mg/m². Doses were alternately escalated at each step by 10 mg/m² for both drugs. Filgrastim 300 g/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/m² and 100 mg/m², 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.This work is presented on behalf of the Southern Italy Cooperative Oncology Group (SICOG), c/o National Tumor Institute of Naples, Italy.