Gemcitabine plus docetaxel as first-line biweekly therapy in locally advanced and/or metastatic urothelial carcinoma: a phase II study.

The purpose of the study was to evaluate objective response rate, survival and toxicity of the combination of gemcitabine-docetaxel administered on a biweekly schedule as first-line treatment in advanced/relapsed or metastatic urothelial carcinoma. Treatment consisted of the sequenced administration of gemcitabine 1500 mg/m(2) and docetaxel 60 mg/m(2) (2 h intravenous infusion) on days 1, 14 of a 28-day cycle for 6 months. A total of 33 patients, 22 men and 11 women, were enrolled, aged 41-75 years (median 64 years). The majority of patients had a good performance status (94%; status<2). Thirteen patients had locally advanced disease (39%) and 20 metastasic disease (41%). A total of 178 treatment cycles were administered with a median number of 5.4 cycles for a patients (range 2-8). Toxicity was primarily hematologic with the most frequent grade >2 being neutropenia (11%), with three episodes of febrile neutropenia. Anemia and thrombocytopenia were milder and had a lower incidence. The most frequent nonhematological toxicities were alopecia, followed by asthenia. Cardiac and pulmonary toxicity was minimal. No toxic deaths were recorded during study and follow-up. Overall response rate was 53.1%, including four complete responses (12.5%) and 13 partial responses (40.6%), whereas six patients (18.8%) had disease stabilization. Median time to progression was 10.2 months (95% confidence interval: 5.1-13.7), with a median survival of 14.8 months (95% confidence interval: 9.4-20.2) after an observation of 30 months (range 4-30+). The results of this study suggested that combination therapy with gemcitabine and docetaxel administered twice a week is particularly active and well tolerated as first-line treatment in advanced and/or metastatic urothelial carcinoma. Once data are confirmed in a larger study and longer follow-up, the favorable toxicity profile of this regimen may offer an interesting alternative to the cisplatin-based regimen.