A phase II trial of neoadjuvant nab-paclitaxel, carboplatin, and gemcitabine (ACaG) in patients with locally advanced carcinoma of the bladder

Objective: To assess the activity of neoadjuvant nab-paclitaxel, carboplatin, gemcitabine (ACaG) followed by cystectomy in patients with muscle-invasive urothelial carcinoma of the bladder. Methods: Patients who were candidates for cystectomy received nab-paclitaxel 260 mg/m² on day 1, carboplatin area under the curve 5 on day 1, and gemcitabine 800 mg/m ² on days 1 and 8, every 21 days for 3 cycles. The first 3 patients received nab-paclitaxel 100 mg/m² weekly and were not included in the efficacy analysis of evaluable patients. Efficacy was assessed by the percentage of patients with pathologic complete response (pT0) at cystectomy. Progression-free and overall survival was estimated using the Kaplan-Meier methods. Results: Of 29 patients enrolled, 26 received the planned 3 cycles with 82 cycles overall; doses were reduced in 16 patients. Of 29 patients, nearly all patients experienced grade 3-4 neutropenia; 17 patients (58.6%) required growth factor, and 16 patients (55.2%) experienced grade 3-4 thrombocytopenia; there was 1 toxicity-related death. Nonhematological toxicity was generally tolerable. Twenty-two of 26 patients were evaluable for the primary endpoint: 6 patients (27.3%, 95% confidence interval [CI] 10.7-50.2) had pT0, 6 pTis, 1 pT1, 54.5% of patients had no residual muscle-invasive disease (<pT2N0), and 81.8% had pN0 at cystectomy. By intent-to-treat (ITT) analysis, the pT0 rate was 27.6% (95% CI 12.7-47.2). Conclusion: Neoadjuvant nab-paclitaxel, carboplatin, gemcitabine is feasible but grade 3-4 myelotoxicity is common. Although the regimen has activity, the pT0 rate is lower than those reported with cisplatin-based regimens and did not meet the predefined threshold to support further investigation. Taxane-based regimens remain investigational for neoadjuvant therapy of bladder cancer.