Phase II trial of adjuvant gemcitabine plus cisplatin-based chemotherapy in patients with locally advanced bladder cancer.

Background: Despite the general acceptance of gemcitabine/cisplatin in metastatic bladder cancer, its role and tolerability in the adjuvant setting, in which renal insufficiency is common, is unclear.

Patients And Methods: A total of 39 patients with locally advanced transitional cell carcinoma of the bladder (T2-T4, N0-N2) were treated with 4 cycles of gemcitabine/cisplatin/amifostine after radical cystectomy. All toxicities were evaluated by the National Cancer Institute Common Toxicity Criteria. Tumor samples were immunohistochemically stained for pRB, p53, and p16.

Results: Thirty-five patients (90%) completed 4 cycles of chemotherapy. Eleven patients (28%) experienced grade 4 hematologic toxicity, and 14 patients (36%) experienced grade 3 nonhematologic toxicity. The median increase in creatinine was 0.3 mg/dL. With a median follow-up of 22.8 months (range, 7-70 months), 13 patients (33%) had recurrent disease, 1 patient at 6 years after completion of therapy. Twelve patients (31%) died, including 11 (28%) with recurrent disease. Thirty-three tumor blocks were evaluated for pRB, p53, and p16 alterations. In an exploratory analysis, altered expression of p53, p16, and pRB was found in 15 (45%), 22 (67%), and 30 patients (91%), respectively. No association between altered p53 and disease-free or overall survival was detected, but altered p16 and pRB expression was associated with better outcome (P < or = 0.001).

Conclusion: Gemcitabine/cisplatin with amifostine is tolerated in the adjuvant setting for patients with locally advanced bladder cancer. The favorable prognostic value of altered p16 and pRB raises the hypothesis of a relative beneficial effect of chemotherapy in this population but needs verification in other studies.