1666 SWOG S0353 PHASE II TRIAL OF INTRAVESICAL GEMCITABINE IN PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER WHO RECURRED FOLLOWING AT LEAST TWO PRIOR COURSES OF BCG

Abstract

INTRODUCTION AND OBJECTIVES: The optimal treatment for patients with intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) who have recurred following intravesical BCG therapy is unclear. Gemcitabine has good activity against urothelial cancer when used systemically, and prior Phase I & II studies have shown it to be active and well tolerated when used intravesically. However, durable responses following a single 6-week induction course have been observed in 30% of high-risk patients. SWOG performed a multi-institutional phase II study to evaluate the potential role of gemcitabine induction plus maintenance therapy in this setting. METHODS: Eligible patients had recurrent NMIBC, stage Tis, T1, Ta high-grade (HG), or Ta low-grade (LG) with 2 lesions, following a minimum of 2 prior courses of intravesical BCG therapy (6 6 weeks or 6 3 weeks, with or without maintenance). Prior single dose peri-operative chemotherapy and up to 1 course of weekly intravesical chemotherapy within the prior year were allowed. All visible lesions were resected and patients were treated with 2gm gemcitabine in 100cc NS weekly x6 and then monthly to 12 months. Patients had bladder biopsy at the initial 3-month evaluation following induction, and then were followed with cystoscopy and cytology every 3 months with further biopsies as clinically indicated. Initial response required negative cystoscopy, cytology and biopsy at 3 months. RESULTS: 58 patients were enrolled; 9 were ineligible and 2 received no treatment. Of 47 evaluable patients, 41 (87%) had high-risk disease, with HGTa in 11 (23%), HGT1 in 2 (4%), and Tis in 28 (8 with and 20 without associated papillary lesions). All patients have been followed a minimum of 12 months. Thirty patients had G1-2 toxicity, mostly dysuria and urinary frequency, while 3 had G3 toxicity (dysuria, frequency and neutropenia). At the initial 3-month evaluation, 21 (45%) patients were free of disease while 13 patients were continuously disease free at 12 months (28% of evaluable patients and 62% of the initial responders). CONCLUSIONS: Intravesical gemcitabine has activity in high risk BCG refractory NMIBC. However, only a minority of patients with intermediate to high-risk disease who have recurred after 2 prior courses of intravesical BCG will attain a durable response to this treatment, even with the addition of monthly maintenance treatments.