Phase II trial of gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive bladder cancer: Preliminary results

Abstract

14590 Background: Gemcitabine and cisplatin (GC) is an active and well tolerated combination in the treatment of metastatic bladder cancer (BC). Studies of neoadjuvant chemotherapy in BC suggest improved survival, especially for patients with complete pathologic response. We have prospectively analyzed the tolerability and efficacy of GC as neoadjuvant treatment of invasive BC. Methods: in this single-institution, one-stage phase II trial, patients (pts) with histologically verified muscle-invasive transitional cell carcinoma received 3 cycles of gemcitabine 1200 mg/m2 on days 1 and 8 with cisplatin 75 mg/m2 on day 1 prior to surgery. Radiologic response was evaluated with computed tomography and magnetic resonance imaging. Planned accrual was 35 pts. Primary endpoint was clinical and pathological response rate. Results: between Jun 2002 and Mar 2005, 22 pts (19 males) were enrolled. Accrual was poor due to a higher percentage of superficial tumors than expected. Median age was 61 years. All pts had Performance Status 0 or 1. Initial stage was II (T2) in 11 and III (T3–4) in 11 pts. Chemotherapy was well tolerated with infrequent grade III/ IV toxicity (nausea/ vomiting in 27%, neutropenia in 23% and neutropenic fever in 1 patient). Median follow-up is 26 months (6–40). Partial radiologic response rate was documented in 15 out of 19 assessable pts (79%). One patient was excluded due to renal toxicity in the first chemotherapy cycle and other had sarcomatoid carcinoma at definitive pathologic examination. By Dec 2005, 14 pts underwent radical cystectomy, 4 pts pelvic radiotherapy, 1 is waiting surgery and 1 had systemic progression before surgery. Nine out of 20 pts (45%) relapsed (8 systemic and 1 local) and 4 (20%) are dead (3 with confirmed disease progression). Complete pathologic response was observed in 3 pts (21.5% of 14) and local progression during chemotherapy in another 3 pts. Median estimated progression-free survival by Kaplan-Meier is 27 months (CI 95% 20.5–33.5) with median overall survival not reached. Conclusions: the combination of gemcitabine and cisplatin is effective and tolerable when used as neoadjuvant therapy in muscle-invasive bladder cancer. Longer follow-up is necessary to evaluate its impact in the overall survival of these pts. [Table: see text]