title: 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.
abstract: 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).
  
  
  METHODS
  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), > or = pT2 disease, or intraoperative complications, patients were discontinued.
  
  
  METHODS
  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 > or = 20 h. A second TUR (no instillation) and adjuvant bacillus Calmette-Guérin (BCG) instillations were allowed.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Urology, Helios Agnes Karll Hospital, Bad Schwartau, Germany.
authors: Andreas
authors: A
authors: Böhle
authors: Herbert
authors: H
authors: Leyh
authors: Christian
authors: C
authors: Frei
authors: Michael
authors: M
authors: Kühn
authors: Reinhold
authors: R
authors: Tschada
authors: Tobias
authors: T
authors: Pottek
authors: Walter
authors: W
authors: Wagner
authors: Helmut H
authors: HH
authors: Knispel
authors: Wolfgang
authors: W
authors: von Pokrzywnitzki
authors: Ferruh
authors: F
authors: Zorlu
authors: Karin
authors: K
authors: Helsberg
authors: Birgit
authors: B
authors: Lübben
authors: Victoria
authors: V
authors: Soldatenkova
authors: Clemens
authors: C
authors: Stoffregen
authors: Hartwig
authors: H
authors: Büttner
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011182:Postoperative Care; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine