title: Incidence and predictors of urotoxic adverse events in cyclophosphamide-treated patients with systemic necrotizing vasculitides.
abstract: OBJECTIVE
  To assess hemorrhagic cystitis and urinary tract cancer incidence and predictors in cyclophosphamide (CYC)-treated patients with systemic necrotizing vasculitis (SNV).
  
  
  METHODS
  The French Vasculitis Study Group database, which contains longitudinal data on SNV patients, was searched for urinary tract cancer and/or hemorrhagic cystitis occurrences in patients diagnosed as having Wegener's granulomatosis (WG), microscopic polyangiitis, Churg-Strauss syndrome, or polyarteritis nodosa. The observed incidence of urinary tract cancer was compared to the expected incidence in the general population by calculating standardized incidence ratios (SIRs). Relationships between urinary tract cancer and/or hemorrhagic cystitis and 10 variables, including CYC dosage and administration route, were investigated by survival analyses for a nested subgroup of patients for whom detailed information on CYC exposure was available.
  
  
  RESULTS
  Among the 805 patients observed over 4,230 patient-years (mean followup 5.3 years), 22 cases of hemorrhagic cystitis and 7 of urinary tract cancer were identified in 27 patients. The SIRs for urinary tract cancer were 5.00 for all patients with SNV (P = 0.001) and 5.96 for patients with WG (P = 0.03). Based on 467 patients with detailed CYC information, cumulative CYC dose (hazard ratio [HR] for 10-gm increments 1.09; P = 0.03), ever-oral CYC administration (HR 5.50; P = 0.001), and WG (HR 2.96; P = 0.01) independently predicted urinary tract cancer and/or hemorrhagic cystitis. According to univariate analyses, smoking (ever) (HR 8.20; P = 0.02) and a prior hemorrhagic cystitis episode (HR 5.20; P = 0.046) significantly predicted urinary tract cancer.
  
  
  CONCLUSIONS
  Our findings indicate that CYC treatment of SNV is associated with a 5-fold higher risk of developing urinary tract cancer. Urotoxicity risk in SNV is associated with the cumulative CYC dose and its oral administration, and might be higher in WG.
authors.affiliation: Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, and Université Paris 5, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Le Guenno
authors.forename: Alfred
authors.initials: A
authors.lastname: Mahr
authors.forename: Christian
authors.initials: C
authors.lastname: Pagnoux
authors.forename: Robin
authors.initials: R
authors.lastname: Dhote
authors.forename: Loïc
authors.initials: L
authors.lastname: Guillevin
mesh_terms: D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000009:adverse effects*; D003556:Cystitis / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012306:Risk; D012307:Risk Factors; D056647:Systemic Vasculitis / Q000188:drug therapy*; D014571:Urologic Neoplasms / Q000453:epidemiology* / Q000209:etiology
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide