Phase II trial of paclitaxel, carboplatin and gemcitabine in patients with locally advanced carcinoma of the bladder.

PURPOSE

This 2-arm phase II multicenter trial was designed to assess the efficacy and toxicity of neoadjuvant paclitaxel, gemcitabine and carboplatin in patients with invasive bladder cancer.

MATERIALS AND METHODS

Patients in arm I had clinical stage T2 with hydronephrosis or T3 bladder cancer. They received 3 cycles of chemotherapy (200 mg/m(2) paclitaxel on day 1, AUC 5 carboplatin on day 1, and 800 mg/m(2) gemcitabine on days 1 and 8 of each 21-day cycle). Response was defined as achievement of a pathological complete response (pT0). Patients in arm II with T4 or lymph node positive disease received up to 6 cycles of paclitaxel, carboplatin and gemcitabine. Response was defined as conversion to surgical resectability.

RESULTS

In arm I, 31 patients were enrolled and 22 were evaluable for response. Seven patients had pT0 disease (32% of evaluable patients, 22% by intent to treat). In arm II, 37 patients were enrolled and 29 were evaluable for response with 24 suitable for surgical resection (83% of evaluable and 65% by intent to treat). The most common toxicity was neutropenia with 39 events in arm I and 68 in arm II. There were 7 deaths on study (5 during chemotherapy and 2 after cystectomy).

CONCLUSIONS

Neoadjuvant paclitaxel, carboplatin and gemcitabine resulted in a significant number of responses in both arms but greater than anticipated toxicity. The pT0 rate was modest and overall efficacy was difficult to assess due to the toxicity. More studies of novel agents and combinations are needed to improve the efficacy and reduce the toxicity of neoadjuvant therapy for bladder cancer.