A Phase II Trial of Neoadjuvant ABI-007, Carboplatin, and Gemcitabine (ACG) in Patients with Locally Advanced Carcinoma of the Bladder.

244 Background: Neoadjuvant cisplatin-based chemotherapy benefits patients with bladder cancer, particularly in the 30% with pathologic complete response (pCR) at cystectomy. Many patients with bladder cancer are not candidates for cisplatin. Taxane-based regimens have activity in urothelial cancer. ABI-007 is an albumin-bound paclitaxel with increased activity and decreased toxicity compared to standard paclitaxel preparations. Methods: Eligible pts have T2-4,N0,M0 or Tany,N1- 3,M0 bladder cancer with ECOG PS 0-1, and adequate marrow (granulocyte count > 1,500/mm3, platelet > 100,000/mm3, and hemoglobin > 9.0 g/dl), hepatic (transaminases < 2.5 X upper limit of normal, alkaline phosphatase < 2.5 X upper limit of normal, and bilirubin < 1.5 mg/dl) and renal function (serum creatinine < 2.0 mg/dl and/or creatinine clearance > 40 ml/min). Pts are treated with intravenous ABI-007 260 mg/m2 and carboplatin (target area under the curve=5) on day 1 with gemcitabine 800 mg/m2 on days 1 and 8, followed by radical cystectomy after three cycles of therapy. The primary study endpoint is the proportion of patients with pCR at cystectomy. Results: 27 patients have been enrolled. By clinical staging, 20 had T2 disease, 5 had T3, 2 had T4, and 2 had nodal enlargement. All are evaluable for toxicity with 22 evaluable for response (exclusions-3 for change in dose schedule, 1 each for refusal of cystectomy and withdrawal from study). 25/27 patients received all three cycles (78 total cycles) with doses reduced in 26 cycles for toxicity. All patients had transient grade 3-4 neutropenia and 17 received filgrastim, but only two had febrile neutropenia. Six pts had pCR with an additional 5 having residual carcinoma in situ (CIS) and 1 with T1 disease at cystectomy. 54% of evaluable patients had no muscle invasive disease at cystectomy. Conclusions: Neoajuvant ACG is active in bladder cancer with pCR rate nearing 30% and nearly as many patients with CIS but no residual invasive disease. Marrow toxicity is significant but manageable. [Table: see text]