Phase II trial of neoadjuvant cisplatin, gemcitabine, and bevacizumab followed by radical cystectomy (RC) in patients with muscle-invasive transitional cell carcinoma (TCC) of the bladder.

Abstract

276 Background: Cisplatin-based neoadjuvant chemotherapy has shown survival advantage in patients (pts) with muscle-invasive bladder cancer. This benefit is strongly associated with downstaging of tumor to pT0. It was hypothesized that the addition of antiangiogenic therapy bevacizumab (Avastin [A]) to cisplatin (C) and gemcitabine (G) chemotherapy may offer improved outcomes in these pts. Methods: Patients with clinically localized, muscle-invasive, chemotherapy-naive TCC of bladder (T2-T4a), ECOG PS 0-1 received cisplatin 70 mg/m2 IV day 1, gemcitabine 1000 mg/m2 IV day 1 and 8, bevacizumab 15 mg/kg IV day 1 on a 21- day cycle for up to 4 cycles. After completion of neoadjuvant therapy all pts underwent RC. Those pts not achieving pT0 status received paclitaxel 175 mg/m2 IV day 1 and bevacizumab 15 mg/m2 IV day 1 on a 21-day cycle for up to 3 cycles. The primary objective of the trial was to achieve pT0 status. Results: By October 2010, 15 pts were enrolled, and 13 are evaluable for response. Median age was 64 (range 47-71), 9 (70%) males, 4 (30%) females. 2/13 (15%) developed PD after neo-adjuvant therapy and were taken off protocol.11/13 (85%) underwent RC. 4/13 (31%) pts were downstaged, 3/11 (27%) achieved pTis status and none achieved pT0 status. 2/11 (18%) pts received adjuvant paclitaxel chemotherapy with bevacizumab. Dose reduction or delays were noted in 12/15 (80%) pts. Grade 3 or 4 hematologic toxicity was observed in 5/15 (33%) pts. Grade 3 or 4 nonhematologic toxicity was observed in 3/15 (20%) pts: (renal dysfunction 2 pts, pulmonary embolism 1 pt). Postoperative complications were seen in 5/12 (42%) pts: enterovesicular fistula (1), delayed wound healing (1), prolonged ileus (2), and pelvic abscess (1). With a median follow-up time of 12 months (range 3-45), 8/11 (72%) pts have remained disease free. Conclusions: Neoadjuvant CGA is feasible in pts with clinically localized, muscle-invasive TCC of the bladder. The surgical complications rate appears rather high and close monitoring is needed. Accrual to the trial continuous and updated results will be presented. No significant financial relationships to disclose.