title: Cancer risk after cyclophosphamide treatment in idiopathic membranous nephropathy.
abstract: OBJECTIVE
  Cyclophosphamide treatment improves renal survival in patients with idiopathic membranous nephropathy. However, use of cyclophosphamide is associated with cancer. The incidence of malignancies in patients with idiopathic membranous nephropathy was evaluated, and the cancer risk associated with cyclophosphamide use was estimated.
  
  
  METHODS
  Patients who attended the clinic were included prospectively from 1995 on. A crude incidence ratio for the occurrence of malignancy was calculated. Incidence ratios were subsequently standardized to potential confounders. Latency between cyclophosphamide therapy and the occurrence of cancer was estimated by stratifying for time since the start of treatment. Finally, Poisson regression was used to obtain a multiple adjusted incidence ratio and investigate the dose-response relationship between cyclophosphamide and cancer.
  
  
  RESULTS
  Data were available for 272 patients; the mean age was 51 years, and 70% of the patients were men. Median follow-up was 6.0 years (interquartile range=3.6-9.5), and 127 patients were treated with cyclophosphamide. Cancer incidence was 21.2 per 1000 person-years in treated patients compared with 4.6 per 1000 person-years in patients who did not receive cyclophosphamide, resulting in crude and adjusted incidence ratios of 4.6 (95% confidence interval, 1.5 to 18.8) and 3.2 (95% confidence interval, 1.0 to 9.5), respectively.
  
  
  CONCLUSIONS
  Cyclophosphamide therapy in idiopathic membranous nephropathy gives a threefold increase in cancer risk. For the average patient, this finding translates into an increase in annual risk from approximately 0.3% to 1.0%. The increased risk of malignancy must be balanced against the improved renal survival.
authors.affiliation: Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands Jan.vandenBrand@radboudumc.nl.
authors.forename: Jan A J G
authors.initials: JA
authors.lastname: van den Brand
authors.affiliation: Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Peter R
authors.initials: PR
authors.lastname: van Dijk
authors.affiliation: Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Hofstra
authors.affiliation: Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
mesh_terms: D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D016012:Poisson Distribution; D011446:Prospective Studies
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
keywords: GN; anti-phospholipase A2 receptor antibodies; cancer incidence; cohort study; cyclophosphamide; dose response relation; latency; malignancy; membranous nephropathy