A Phase II Trial of Neoadjuvant nab-paclitaxel, Carboplatin, and Gemcitabine (ACaG) in Patients With Locally Advanced Carcinoma of?the Bladder

详细信息    查看全文

• 作者：Petros D. Grivas ; Maha Hussain ; Khaled Hafez ; Stephanie Daignault-Newton ; David Wood ; Cheryl T. Lee ; Alon Weizer ; James E. Montie ; Brent Hollenbeck ; Jeffrey S. Montgomery ; Ajjai Alva ; David C. Smith
• 刊名：Urology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：82
• 期：1
• 页码：111-117
• 全文大小：311 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

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 (<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.