title: [Prevention of topic toxicity of BCG with single-dose prulifloxacin. Preliminary results of a randomized pilot study].
abstract: BACKGROUND
  Toxicity is a major problem for patients undergoing intravesical therapy with Bacillus Calmette-Guérin (BCG) for the conservative management of intermediate or high-risk non-muscle invasive bladder cancer (NMI-BC). A prospective pilot trial was designed to evaluate the adoption of a single dose of prulifloxacin to prevent the toxicity of BCG. Treatment tolerability and its possible influence on BCG efficacy have been analyzed.
  
  
  METHODS
  The study was designed to evaluate the action of prulifloxacin in patients with intermediate or high-risk NMI-BC, undergoing 6-week induction cycle of BCG. Main exclusion criteria were previous intravesical therapy, urinary infection and any other factor that could influence tolerability to BCG intravesical immunotherapy. The patients were randomized to receive BCG alone versus BCG plus prulifloxacin. BCG toxicity and local tolerability were evaluated by self-administered EORTC QLQ-BLS24 questionnaire, and BCG adverse events (AEs) were classified according a four-class classification. The toxicity and tolerability evaluations were performed at baseline, one week after every instillation and one week and one month after the last instillation. Cystoscopy and cytology were performed 3-monthly. Recurrence and progression were recorded.
  
  
  RESULTS
  The study included 43 patients receiving 258 instillations of BCG. The patients were randomized to receive BCG alone (Arm A: 132 instillations in 22 patients) versus BCG plus prulifloxacin given as a single oral dose (600 mg) 6 hours after the instillation. An advantage in favor of prulifloxacin prophylaxis emerged, according to EORTC QLQ-BLS24, in overall incidence of nocturnal micturitions (56% vs 28.6%; p=0.001), insomnia (40% vs 14.3%; p=0.002), urgency (70% vs 42.6%; p=0.05), incontinence (44% vs 12.7%; p=0.01) and bothersome events due to intravesical therapy (84% vs 63.5%; p=0.02). Systemic class IIB and III adverse events occurred in only 14.2% and 3.5% of the patients, respectively. No class IV AE was detected. Due to the low incidence no statistically significant difference was evident between the two arms (p=0.6). Three patients of Arm B and 1 patient of Arm A interrupted the treatment, after the 3rd - 4th instillation. Anti-tuberculosis therapy war required for 3 months in only one patient. Three and 2 instillations were postponed for one-(two) week(s) in Arm B and Arm A, respectively. Prulifloxacin, generally well tolerated, was withdrawn in one patient due to skin allergic reaction. Recurrence rate at a mean follow-up of 12 months did not significantly differ between the two arms.
  
  
  CONCLUSIONS
  Prulifloxacin decreases the incidence of local symptoms and improves the compliance to BCG intravesical therapy. Due to the low number of events, no evidence emerges in our study about its capability of preventing severe systemic toxicity, although it has proved effective in reducing local symptoms.
authors.affiliation: Sezione di Urologia, Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefro-Urologiche Università degli Studi di Palermo, Italy. vserretta@libero.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Serretta
authors.forename: Antonina
authors.initials: A
authors.lastname: Ruggirello
authors.forename: Rosellina
authors.initials: R
authors.lastname: Giaimo
authors.forename: Francesco
authors.initials: F
authors.lastname: Sommatino
authors.forename: Valentina
authors.initials: V
authors.lastname: Billone
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Allegro
authors.forename: Darvinio
authors.initials: D
authors.lastname: Melloni
mesh_terms: D000283:Administration, Intravesical; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy; D004148:Dioxolanes / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010349:Patient Compliance; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy; D014555:Urination Disorders / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control
chemical_list: D001500:BCG Vaccine; D004148:Dioxolanes; D024841:Fluoroquinolones; D010879:Piperazines; C074191:prulifloxacin