INTRAVESICAL INSTILLATION OF GEMCITABINE NOT EFFECTIVE FOR BLADDER CARCINOMA

Eur Urol. 2009 Jun 21. [Epub ahead of print]

Related Articles, LinkOut

Single Postoperative Instillation of Gemcitabine in Patients with Non-muscle-invasive Transitional Cell Carcinoma of the Bladder: A Randomised, Double-blind, Placebo-controlled Phase III Multicentre Study.

Böhle A, Leyh H, Frei C, Kühn M, Tschada R, Pottek T, Wagner W, Knispel HH, von Pokrzywnitzki W, Zorlu F, Helsberg K, Lübben B, Soldatenkova V, Stoffregen C, Büttner H; on behalf of the S274 Study Group.

Department of Urology, Helios Agnes Karll Hospital, Bad Schwartau, Germany (on behalf of the German AUO Trial Group).

BACKGROUND: Recurrence prophylaxis with intravesical gemcitabine (GEM) was effective and safe in patients with non-muscle-invasive bladder cancer (NMIBC); efficacy as single-shot instillation remains to be proved. OBJECTIVE: To compare the efficacy of a single GEM instillation versus placebo (PBO) immediately after transurethral resection (TUR) of tumour in patients with histologically confirmed NMIBC (pTa/pT1,G1-3). DESIGN, SETTING, AND PARTICIPANTS: This was a double-blind, randomised, PBO-controlled study in patients with clinical evidence of primary or recurrent NMIBC (Ta/T1,G1-3). Of 355 patients randomised at 24 urologic centres, 328 underwent TUR and received instillation (92.4%; GEM/PBO: 166/162). In case of nonmalignancy, carcinoma in situ (CIS), >/=pT2 disease, or intraoperative complications, patients were discontinued. INTERVENTION: We used a single, postoperative 30-40-min instillation of GEM (2000mg/100ml of saline) or PBO (100ml of saline) followed by continuous bladder irrigation for >/=20h. A second TUR (no instillation) and adjuvant bacillus Calmette-Guérin (BCG) instillations were allowed. MEASUREMENTS: Primary outcome was recurrence-free survival (RFS). Secondary outcomes included type of recurrence and adverse events. To detect a difference in RFS, 191 recurrences were required (80% power, log-rank-test, alpha=0.050). RESULTS AND LIMITATIONS: Two hundred forty-eight patients (69.9%, GEM, PBO: 124, 124) had histologically confirmed pTa/pT1 G1-3 Gx tumour and were eligible for efficacy (GEM: 76.6% male; median age: 65 yr; PBO: 83.1% male; median age: 67 yr). Treatment groups were balanced (pTa: 75.0%, 71.0%; G1-G2: 85.5%, 87.9%; recurrent tumour: 24.2%, 21.0%; BCG: 10.5%, 16.9%). After a median follow-up of 24 mo, there were only 94 recurrences and 11 deaths. The study was terminated early based on predefined decision criteria. RFS was high in both groups (12-mo RFS [95% confidence interval (CI)]: GEM: 77.7% [68.8-84.3]; PBO: 75.3% [66.3-82.3]). There was no significant group difference (hazard ratio [HR]: 0.946 [0.64-1.39], log-rank test, p=0.777). CONCLUSIONS: In this study of NMIBC, the immediate single instillation of GEM 2000mg/100ml of saline after TUR was not superior to PBO in terms of RFS. Rigid continuous irrigation and improved TUR/cystoscopy techniques may have contributed to the high RFS in both groups.