Paclitaxel and gemcitabine as salvage treatment in metastatic breast cancer.

Both paclitaxel and gemcitabine (Gemzar) have shown activity and manageable toxicity when used as single agents in heavily pretreated patients with metastatic breast cancer. This phase II study evaluated their use in combination for metastatic breast cancer patients whose disease recurred or progressed following treatment with anthracycline-containing regimens. Twenty-nine patients ranging from 32 to 68 years of age received paclitaxel at 175 mg/m2 i.v. over 3 hours on day 1 and gemcitabine at 1,000 mg/m2 i.v. on days 1, 8, and 15 every 28 days. Because of unacceptable thrombocytopenia in the first five patients, the gemcitabine schedule was changed to days 1 and 8 of a 21-day cycle for the remainder of the study. All 29 patients were evaluable for response and toxicity. Seventeen patients (59%) were considered truly anthracycline- or anthracenedione-refractory. A total of 137 cycles (median: 4 per patient) were administered. The regimen was well tolerated. Grade 3/4 thrombocytopenia was observed in 5 (18.5%) of the first 27 cycles and in 6 (5.4%) of the 110 cycles following dosage reduction (P = .04). Five patients had grade 1 and two patients had grade 3 neuropathy. Eight patients had grade 3 neutropenia, two had grade 4 neutropenia with fever at the higher dosage, and eight had grade 1/2 myalgia and fatigue. Five patients (17%) had a complete response and 11 (38%) a partial response, yielding an objective response rate of 55% (95% confidence interval = 36%-73%). Six patients (20.7%) had stable disease. Median response duration was 8 months (range: 4-26 months), and median overall survival was 12 months (range: 4-48+ months). Survival at 1, 2, 3, and 4 years was 45%, 30%, 20%, and 10%, respectively. The combination of paclitaxel on day 1 with gemcitabine on days 1 and 8 of a 21-day cycle appears to have promising activity in heavily pretreated patients with metastatic breast cancer. Phase III trials comparing this promising doublet to paclitaxel monotherapy and to other chemotherapeutic strategies for advanced breast cancer will clarify the role of this regimen.