Southwest oncology group study of paclitaxel and carboplatin for advanced transitional-cell carcinoma: The importance of survival as a clinical trialend point

Purpose: The combination of paclitaxel and carboplatin for the treatment of advanced transitional-cell carcinoma (TCC) of the urothelium has promising activity and acceptable toxicity. The purpose of this trial was to evaluat e the efficacy of this regimen in a cooperative group setting. Patients and Methods: Twenty-nine patients with advanced TCC were treated e very 21 days with paclitaxel 200 mg/m(2), administered as a 3-hour infusion , followed by carboplatin dosed ta an area under the curve of 5, Prior syst emic adjuvant or neoadjuvant platinum-based therapy was not permitted unles s completed at least 1 year before enrollment. Patients were evaluated for response every three cycles, and follow-up was conducted to determine survi val. Results: Twenty-nine patients were enrolled and were assessable. Four (14%) had received prior adjuvant or neoadjuvant therapy, Node-only disease was present in 24%, and 76% of patients had extranodal disease. The median numb er of cycles received was five. Grade 4 toxicity consisted primarily of neu tropenia (38% of patients). Neurologic toxicity was noted in 16 patients (g rade 1 in four patients, grade 2 in five patients, grade 3 in six patients, and grade 4 in one patient), Six partial responses and no complete respons es were noted, for a response proportion of 20.7% (95% confidence interval, 8% to 40%). Median progression-free survival time was 4 months, and overal l survival time was 9 months. Conclusion: The combination of paclitaxel and carboplatin for the treatment of advanced TCC is reasonably well tolerated. However, ct response proport ion considerably lower than that previously reported was noted. In addition , the median survival time of 9 months wens less than the survival time pre viously reported for patients treated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin, Although our results may reflect enrollment of patients with poor prognostic features, they also call into q uestion the utility of this regimen. J Clin Oncol 18:2537-2544. (C) 2000 by American Society of Clinical Oncology.