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

Abstract

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.

Weekly Docetaxel and Gemcitabine as First-Line Treatment for Metastatic Breast Cancer: Results of a Multicenter Phase II Study

“…In our dose-finding study [19], 18 heavily pretreated patients received 3 escalating weekly doses of docetaxel (30, 35 and 40 mg/m 2 ) with a weekly fixed dose of gemcitabine 800 mg/m 2 on days 1, 8 and15 of a 28-day cycle. The MTD for docetaxel was reached at the 40 mg/m 2 dose and the recommended dose for subsequent phase II studies was established at the 35 mg/m 2 dose.…”

“…The MTD for docetaxel was established at 35 mg/m 2 . Hematological and nonhematological toxicities were low in number and manageable [19]. With this background, we conducted a multi-institutional phase II study, whose data were partially presented in an abstract form [20], to evaluate the clinical efficacy, the toxicity pattern and the dose-intensity of a new weekly regimen of docetaxel and gemcitabine.…”

Weekly docetaxel in the treatment of metastatic breast cancer

“…In order to determine the maximum tolerable dose of docetaxel in association with gemcitabine, both given on a weekly schedule, Brugnatelli et al designed a phase I study using three escalating doses of docetaxel (30, 35, and 40 mg/m 2 ) followed by a fixed dose of gemcitabine, 800 mg/m 2 , on days 1, 8, and 15 of a 28-day cycle (Brugnatelli et al 2002). Asthenia, stomatitis, and leukopenia were the main DLTs.…”

Weekly Administration of Docetaxel and Paclitaxel in Metastatic or Advanced Breast Cancer

“…Phase I and phase II trials have assessed weekly docetaxel regimens in combination with anthracyclines [41][42][43][44], gemcitabine (Gemzar ® ; Eli Lilly and Company, Indianapolis, http://www.lilly.com) [45][46][47][48][49], vinorelbine (Navelbine ® ; GlaxoSmithKline, Philadelphia, http://www.gsk.com) [46,50], and trastuzumab (Herceptin ® ; Genentech, Inc., South San Francisco, CA, http://www.gene.com) [51]. The combination of two inhibitors of microtubule function, docetaxel and estramustine (Emcyt ® ; Pfizer Pharmaceuticals, New York, http://www.pfizer.com) proved to be too toxic to be investigated further [52].…”