title: The effect of ofloxacin on bacillus calmette-guerin induced toxicity in patients with superficial bladder cancer: results of a randomized, prospective, double-blind, placebo controlled, multicenter study.
abstract: OBJECTIVE
  We determined whether prophylaxis with ofloxacin could decrease the toxicity of bacillus Calmette-Guerin for transitional cell carcinoma of the bladder. We also investigated the impact of ofloxacin on bacillus Calmette-Guerin antitumor efficacy.
  
  
  METHODS
  In this randomized, double-blind, multicenter study 115 patients with primary or recurrent superficial bladder cancer (Ta/T1, CIS, G1-G3) and no prior bacillus Calmette-Guerin treatment were randomized to induction treatment with intravesical bacillus Calmette-Guerin (6 plus 3 instillations) plus 200 mg ofloxacin in group 1 or plus placebo in group 2. Adverse events were assessed using a detailed grid of classification for bacillus Calmette-Guerin related adverse events. Mean patient age +/- SD was 65.6 +/- 10.4 years in the 57 group 1 patients and 65.7 +/- 8.7 years in the 58 in group 2. Median followup was 369 and 374 days in groups 1 and 2, respectively.
  
  
  RESULTS
  Ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate and severe adverse events between instillations 4 and 6. The percent of class III adverse events was significantly decreased by ofloxacin between instillations 1 and 9. Although ofloxacin decreased adverse events involving the lower urinary tract, it did not prevent class I adverse events. Compliance with full bacillus Calmette-Guerin treatment was also improved. Of patients in group 1, 80.7% received 9 instillations compared with 65.5% in group 2 (p = 0.092). At 12 months recurrence and progression rates in group 1 and 2 were 12.7% and 17.2%, and 5.5% and 1.7%, respectively.
  
  
  CONCLUSIONS
  Prophylactic ofloxacin decreased the incidence of moderate to severe adverse events associated with bacillus Calmette-Guerin intravesical therapy, particularly class III events, which are primarily associated with patient dropout. Compliance with induction and maintenance therapy may be improved by adjuvant ofloxacin therapy. However, long-term comparative studies with other preventive strategies must be done to confirm these initial findings with compliance and recurrence-free survival as the primary end points.
authors.affiliation: Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot, Université Claude Bernard, 5. Place d'Arsonval, 69437 Lyon Cedex 03, France. marc.colombel@chu-lyon.fr
authors.forename: Marc
authors.initials: M
authors.lastname: Colombel
authors.forename: Fabien
authors.initials: F
authors.lastname: Saint
authors.forename: Dominique
authors.initials: D
authors.lastname: Chopin
authors.forename: Bernard
authors.initials: B
authors.lastname: Malavaud
authors.forename: Ludovic
authors.initials: L
authors.lastname: Nicolas
authors.forename: Pascal
authors.initials: P
authors.lastname: Rischmann
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000009:adverse effects*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D015242:Ofloxacin / Q000494:pharmacology / Q000627:therapeutic use*; D010865:Pilot Projects; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D001500:BCG Vaccine; D015242:Ofloxacin