Gemcitabine and Paclitaxel Every 2 Weeks in Patients With Previously Untreated Urothelial Carcinoma

BACKGROUND: Patients with urothelial carcinoma are not always amenable to cisplatin-based chemotherapy. The authors previously reported that they achieved a 60% response rate in patients who failed on cisplatin-based combination chemotherapy (methotrexate, vinblastine, doxorubicin, and cisplatin) by using a convenient outpatient regimen of gemcitabine (G) and paclitaxel (P) every 2 weeks. A multicenter trial was initiated in 5 Italian centers to evaluate this regimen as first-line chemotherapy. METHODS: From January 2003 to April 2005, 54 patients who had histologically proven, measurable disease (according to the Response Evaluation Criteria in Solid Tumors) with a World Health Organization (WHO) performance status (PS) from 0 to 2, metastatic or inoperable urothelial carcinoma, no prior systemic cytotoxic or biologic treatment, a creatinine clearance >= 40 mL per minute, and bilirubin <20 mu mol/L received G at a dose of 2500 mg/m(2) in 30 minutes and P at a dose of 150 mg/m(2) in 3 hours every 2 weeks. Granulocyte-colony-stimulating factor (G-CSF) was given for 5 to 7 days for neutropenia toxicity of grade >= 3 (grading determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 guidelines). From 6 to 12 courses were planned. All patients received at least I cycle of therapy and were included in all analyses. RESULTS: The median patient age was 67 years (range 34-78 years), and the median WHO PS was 1 (range, 0-2). Metastases occurred in the lung in 17 patients (31%), in lymph nodes in 26 patients (54%), in the bladder in 20 patients (37%), in bone in 8 patients (15%), and in the liver in 8 patients (15%). Fifty-nine percent of patients had >1 site of disease, and 13% of patients had >= 3 sites of disease. In total, 343 cycles were administered. Five patients achieved a complete response, and 15 patients achieved a partial response; thus, the overall response rate was 37% in an intent-to-treat analysis. Hematologic toxicity was predominant but manageable. G-CSF was used in only 6% of cycles. The median survival was 13.2 months, and the median time to disease progression was 5.8 months. CONCLUSIONS: In a multicenter study, G and P was found to be a well-tolerated outpatient regimen. This regimen demonstrated promise and may be considered in patients who are unable to receive cisplatin. Cancer 2009;115:2652-9. (C) 2009 American Cancer Society.