Adjuvant gemcitabine and cisplatin (GC) for locally advanced cancer of the bladder after radical cystectomy: A USC experience with molecular correlates

Abstract

4639 Background: Invasive bladder cancer has a 50% mortality rate. Adjuvant chemotherapy is used to try to improve survival, but is of unproven benefit. GC and MVAC have similar response rates and survival in the metastatic setting, with GC having less toxicity (JCO 17: 3068). We have used the GC regimen for patients with high grade bladder cancer with poor prognostic features after cystectomy when they have not been candidates for MVAC for medical or personal patient reasons. Methods: We conducted a retrospective study of patients treated with adjuvant chemotherapy between 1997 and 2002. Chemotherapy consisted of 3–4 cycles of adjuvant Gemcitabine 1000mg/m2 (days 1 & 8) and Cisplatin (35mg/m2 days 1 & 2). All patients undergoing radical cystectomy and receiving adjuvant GC at USC were eligible. Medical records were examined and tissues were studied for various molecular markers, including p53, ribonucleotide reductase (RR) and ERCC1. Results: 25 patients met inclusion criteria. Median age was 68; 72% were pT3 or pT4; 68% had lymph nodes involved. All patients had transitional cell carcinoma. P53 was mutated in 75%. The median number of cycles of GC was 3 (84% had 3–4 cycles). 11 patients (44%) had grade 3 or 4 hematologic toxicity and 2 (8%) had grade 3 non-hematologic toxicity. Median follow-up was 25.1 (8.7–49.7) months. 8 patients have died. The median time to recurrence was 49.7 (12.3–49.7+) months with median overall survival of 49.7+ (16.6–49.7+) months. Evaluation of tissue blocks for molecular correlates such as ERCC1 and RR is in progress and will be reported. Conclusions: Adjuvant GC chemotherapy is feasible and effective in the setting of locally advanced bladder carcinoma and will be studied in a prospective, randomized fashion. For the 17 patients with node-positive bladder cancer, adjuvant GC is associated with disease-free median survival of 23.6 (11.3, 49.7+) months and median survival of 23.8+ (16.6, 49.7+) months. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly