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

被引:76
|
作者
Boehle, Andreas [2 ]
Leyh, Herbert [3 ]
Frei, Christian [3 ]
Kuehn, Michael [4 ]
Tschada, Reinhold [5 ]
Pottek, Tobias [6 ]
Wagner, Walter [7 ]
Knispel, Helmut H. [8 ]
von Pokrzywnitzki, Wolfgang [9 ]
Zorlu, Ferruh [10 ]
Helsberg, Karin [1 ]
Luebben, Birgit [1 ]
Soldatenkova, Victoria [1 ]
Stoffregen, Clemens [1 ]
Buettner, Hartwig [1 ]
机构
[1] Lilly Deutschland GmbH, Dept Med, D-61352 Bad Homburg, Germany
[2] Helios Agnes Karll Hosp, Dept Urol, Bad Schwartau, Germany
[3] Klinikum Garmisch Partenkirchen, Dept Urol, Garmisch Partenkirchen, Germany
[4] Johanniter Hosp, Dept Urol, Stendal, Germany
[5] Diakonissenkrankenhaus Mannheim, Dept Urol, Mannheim, Germany
[6] Klinikum Wedel, Dept Urol, Wedel, Germany
[7] Bundeswehrkrankenhaus Hamburg, Dept Urol, Hamburg, Germany
[8] St Hedwig Hosp, Dept Urol, Berlin, Germany
[9] Vivantes Klinikum Urban, Dept Urol, Berlin, Germany
[10] SSK Tepecik Res & Educ Hosp, Yenisehir Izmir, Turkey
关键词
Non-muscle-invasive bladder cancer; Transurethral resection; Gemcitabine; BACILLUS-CALMETTE-GUERIN; TRANSURETHRAL RESECTION; STAGE-TA; INTRAVESICAL GEMCITABINE; DOSE INSTILLATION; URINARY-TRACT; CANCER; EPIRUBICIN; RISK; RECURRENCE;
D O I
10.1016/j.eururo.2009.06.010
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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 (2000 mg/100 ml of saline) or PBO (100 ml of saline) followed by continuous bladder irrigation for >= 20 h. A second TUR (no instillation) and adjuvant bacillus Calmette-Guerin (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 2000 mg/100 ml 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. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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收藏
页码:495 / 503
页数:9
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