Efficacies and safety of neoadjuvant gemcitabine plus carboplatin followed by immediate cystectomy in patients with muscle-invasive bladder cancer, including those unfit for cisplatin: a prospective single-arm study.

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy for patients with muscle-invasive bladder cancer (BC) has better survival benefit than radical cystectomy (RC) alone. However, optimal dosing schedule, including drug selection, number of cycles, and interval between chemotherapy and cystectomy, as well as acceptable regimens remain to be established. We conducted a single-arm prospective study to evaluate efficacy and safety of neoadjuvant gemcitabine plus carboplatin (GCarbo) chemotherapy followed by immediate RC in patients with muscle-invasive BC, including cisplatin-unfit patients.

METHODS: Between March 2005 and June 2011, we enrolled 116 patients with histologically proven muscle-invasive BC, including 44 % of the patients who were identified as cisplatin-unfit. All participants received two courses of GCarbo therapy, gemcitabine 800 mg/m(2) administered on days 1, 8, and 15 and carboplatin with an area under the curve of four (AUC 4) administered on day 2. RC and bilateral pelvic lymphadenectomy were performed approximately within a month after cessation of chemotherapy. The primary endpoint was pT0 in the cystectomy specimen. Secondary endpoints were overall response rate, overall (OS) and disease-free survival (DFS), and toxicity. Survival after cystectomy was analyzed using the Kaplan-Meier method.

RESULTS: The RC specimens of 28 (24.1 %) patients showed pT0. At a median follow-up period of 41 months, the OS and DFS rates were 89.7 and 86.3 %, respectively. No patients had grade 3/4 gastrointestinal toxicity or renal impairment.

CONCLUSIONS: Neoadjuvant GCarbo therapy followed by immediate RC is safe, even in cisplatin-unfit patients, and provides a favorable pathological cancer-free state. The single-arm single-institution study design and relatively short observation period were limitations of this study.