Weekly Administration of Gemcitabine Plus Docetaxel in Patients with Advanced Breast Cancer: A Phase 1 Study

Objective: This study was designed to determine the maximum tolerable dose (MTD) of gemcitabine plus docetaxel, both given on a weekly schedule, in patients with pretreated metastatic breast cancer (MBC). Methods: Heavily pretreated patients with MBC, aged 18–75 years with World Health Organization performance status of 0–2 were enrolled. Three escalating weekly doses of docetaxel (30, 35 and 40 mg/m2) followed by a weekly fixed dose of gemcitabine, 800 mg/m2, were administered on days 1, 8 and 15 of a 28-day cycle. Dose-limiting toxicity (DLT) included grade >3 hematologic toxicity and grade >2 stomatitis, asthenia, diarrhea or organ-specific toxicity (except alopecia). Dose escalation was stopped if ≧3 of 5 patients at any dose level experienced DLT. Results: Eighteen patients (median age 56 years) received a mean of 4.1 (range 1–6) cycles. Asthenia, stomatitis and leukopenia were the main DLTs. One of 5 patients had DLT at dose level 1 and 2 of 5 patients at dose level 2. At dose level 3, 3 of 5 patients had DLTs. Three additional patients treated at dose level 3 confirmed that the MTD had been reached. Therefore, the recommended docetaxel dose in combination with gemcitabine 800 mg/m2 for phase II studies was established at the next lower dose, 35 mg/m2. Of 12 evaluable patients, 7 (58%) achieved an objective response. Conclusions: Gemcitabine 800 mg/m2 plus docetaxel 35 mg/m2 on days 1, 8 and 15 of a 28-day cycle is a safe regimen which shows activity in heavily pretreated patients with MBC. Further phase II investigations with this combination are now warranted.