Neoadjuvant paclitaxel (P), carboplatin (Ca) and gemcitabine (G) in patients with locally advanced transitional cell carcinoma (TCC) of the bladder: A final report

Abstract

4541 Background: PCaG has activity in the treatment of TCC. Studies have shown that neoadjuvant chemotherapy may improve survival in TCC, with pathologic complete responders (pT0) having the most benefit. This study was designed to assess the pT0 rate and resectability following neoadjuvant PCaG in patients with TCC of the bladder. Methods: Patients with adequate organ function, performance status 0–2, and clinical T3 or T2 with hydronephrosis, N0, M0 TCC (Arm I) received 3 cycles of PCaG (P: 200 mg/m2, IV over 3 hours day 1, C: target AUC=5 IV day 1, and G: 800 mg/m2; IV day 1 & 8 every 21 days) followed by cystectomy with a primary endpoint of pT0. T4 or node positive (Tany, N1–3, M0) patients (Arm II) received 6 cycles with an endpoint of resectability. Each arm had a Minimax two-stage accrual with planned initial enrollment of 26 evaluable subjects in arm I (up to 54 total) and 19 in arm II (up to 33). Results: 68 patients were registered (31 arm I, 37 arm II). Median age was 65 years in arm I and 58 years in arm II. 22/31 (71%) patients in arm I are evaluable and 7 were pT0 at cystectomy. pT0 rate is 32% (95% CI: 13.9–54.9%) of evaluable, 23% (9.6–41.1%) by intent to treat (ITT). 30/37 (81%) on arm II are evaluable for response and 20 had cystectomy for a resection rate of 67% (47.2–82.7%) of evaluable, 54% (36.9–70.5%) by ITT. 5 patients resected on arm II had pT0 and 2 had only residual carcinoma in situ. A total of 252 cycles of therapy were delivered (80 in arm I, 172 in arm II) with 161 at full dose. 54/68 patients (79%) had grade 3/4 hematologic toxicity, primarily neutropenia with 4 other episodes of grade 3 toxicity (2-neuropathy, 1-myalgia, 1-fatigue). 4 patients died during chemotherapy (2-bowel obstruction, 1-coronary artery disease, 1-intracranial bleed) and 2 post-op (1-multiorgan failure, 1-enterocolitis). Only 1 death was clearly chemotherapy related, but the study was halted early due to these deaths. Conclusions: Neoadjuvant PCaG has demonstrated activity in locally advanced TCC of the bladder, but has considerable toxicity. The pT0 rate with this combination is comparable to the rates reported in the literature for other regimens. Support from Bristol-Myers Squibb, Eli Lilly, and 2P30 CA 46592–14 from the National Cancer Institute [Table: see text]