Paclitaxel, carboplatin and gemcitabine (PCG) as neoadjuvant therapy in patients with locally advanced transitional cell carcinoma (TCC) of the bladder

Abstract

4541 Background: PCG has substantial activity in the treatment of TCC with lower rates of severe toxicity than MVAC. Recent studies have shown a survival benefit for chemotherapy in the neoadjuvant setting. This study is designed to assess the activity of neoadjuvant PCG in patients with locally advanced TCC of the bladder. Methods: Patients with clinically staged T3, N0, M0 TCC or T2 disease with hydronephrosis (Arm I) receive 3 cycles of PCG (paclitaxel 200 mg/m2, IV over 3 hours day 1, carboplatin target AUC=5 IV day 1, and gemcitabine 800 mg/m2; IV day 1 & 8 every 21 days) and then proceed to cystectomy with an endpoint of pathologic complete response (pCR). Patients with T4 or node positive (Tany, N1–3, M0) disease (Arm II) receive 6 cycles of PCG with an endpoint of conversion to resectability as assessed by the urologist. Results: 49 patients have been entered (26 arm I, 23 arm II). Median age was 65 years in arm I and 56 years in arm II. 23 patients in arm I have completed therapy and 5 (22%) have a pCR. 16/23 patients on arm II have been resected. A total of 187 cycles of therapy have been delivered (65 in arm I, 112 in arm II) and 55% of patients had grade 3/4 hematologic toxicity. Three patients died during therapy, due to previously unrecognized heart disease (1), bowel obstruction (1), and post-cystectomy in a patient with Crohn's disease. Conclusions: Patients treated with PCG achieved a high rate of resectability in locally advanced TCC and a substantial number had pathologic complete response at resection. Hematologic toxicity was acceptable with this regimen with most patients received all cycles of planned therapy. Enrollment to this study is ongoing. Support from Bristol-Myers Squibb, Eli Lilly, and 2P30 CA 46592–14 from the National Cancer Institute Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Bristol-Myers Squibb; Eli Lilly