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 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 μmol/L received G at a dose of 2500 mg/m2 in 30 minutes and P at a dose of 150 mg/m2 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 1 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.
In this multicenter trial, a convenient outpatient regimen of gemcitabine and paclitaxel given every 2 weeks was evaluated as first-line chemotherapy in patients with urothelial carcinoma. The results indicated that the regimen has promise and may be considered for patients who are unable to receive cisplatin and those who have metastatic urothelial cancer and compromised renal function; however, it cannot be recommended for routine use.