Dose escalation study of epirubicin and docetaxel in patients with advanced or recurrent breast cancer.

BACKGROUND: Anthracyclines and taxanes are major cytotoxic drugs against breast cancer. To develop a combination of epirubicin (EPI) and docetaxel (DTX) in Japan, dose escalation and pharmacokinetic studies were performed in patients with advanced or recurrent breast cancer. METHODS: Twenty patients received EPI (40, 50 or 60 mg/m(2)) as 5-min intravenous infusion, followed by DTX infusion (50 or 60 mg/m(2)) over 1 h in cohorts of 3-6 patients. The maximum tolerated dose (MTD) was defined during the first cycle when more than 2 of 3 or 3 of 6 patients suffered a dose-limiting toxicity (DLT). The DLT was based on febrile neutropenia (FN), prolonged neutropenia, thrombocytopenia and grade 3-4 nonhematological toxicity during the first cycle. Plasma sampling was performed to assess the pharmacokinetic study of these drugs. RESULTS: The second level (EPI/DTX 50/50 mg/m(2)) was found to be a maximum tolerated dose because of a short duration of FN with no distress. Subsequently, the protocol was modified to permit a new DLT definition including FN lasting for more than 72 h. At the following levels of EPI/DTX 50/50, 50/60 or 60/60 mg/m(2), the dose escalation study revealed a high incidence of grade 4 neutropenia (100%) and FN (67%), which did not reach DLT. However, the safety committee decided not to go further because of too high an incidence of FN lasting 3 days, although a little less than 72 h. The pharmacokinetic study with a combination of EPI and DTX showed comparable blood levels of DTX and EPI in relation to those seen when given alone. CONCLUSION: For further evaluation, the recommended dose and schedule of this combination is EPI 60 mg/m(2) and DTX 60 mg/m(2), given every 3 weeks to patients without prior chemotherapy and EPI 50 mg/m(2) and DTX 50 mg/m(2) given to patients with prior chemotherapy, respectively. The pharmacokinetic study indicates no interaction between EPI and DTX.

[Pilot study-previously treated advanced non-small cell lung cancer].

This pilot study was performed to evaluate the safety and efficacy of weekly paclitaxel (TXL) administration by 1-hour infusion. A total of 10 patients with previously-treated advanced non-small cell cancer (NSCLC) were treated with weekly paclitaxel. TXL was administered weekly at a dose of 80 mg/m2, 3 times in a 4-week cycle, or 6 times in an 8-week cycle. A total of 6 patients achieved partial response, although no complete responses were observed. Median time to progression was 5 months (2-11 months). Grade 4 leukopenia occurred in one patient, and grade 3 neutropenia was observed in one patient. Severe non-hematological toxicity was uncommon; grade 1 neuropathy in 2 patients. This regimen had good clinical efficacy with low toxicity in outpatients with advanced NSCLC.