A Phase II Trial of Neoadjuvant nab-paclitaxel, Carboplatin, and Gemcitabine (ACaG) in Patients With Locally Advanced Carcinoma of the Bladder
Grivas PD, Hussain M, Hafez K, Daignault-Newton S, Wood D, Lee CT, Weizer A, Montie JE, Hollenbeck B, Montgomery JS, Alva A, Smith DC. Urology. 2013 May 21. pii: S0090-4295(13)00419-6. doi: 10.1016/j.urology.2013.03.044. [Epub ahead of print]

Source

Department of Internal Medicine, Division of Hematology/Oncology, Ann Arbor, MI.

Abstract

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/m2 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 (

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.