title: Effects of cyclophosphamide on the development of malignancy and on long-term survival of patients with rheumatoid arthritis. A 20-year followup study.
abstract: OBJECTIVE
  To examine the effects of cyclophosphamide (CYC) on the development of malignancies and on the long-term survival of patients with rheumatoid arthritis (RA).
  
  
  METHODS
  We used a longitudinal cohort design in which 119 patients (76 women and 43 men) with refractory RA who were treated with oral CYC between 1968 and 1973 were compared with 119 control patients with RA (matched for age, sex, disease duration, and functional class) who were evaluated during the same time period but did not receive CYC.
  
  
  RESULTS
  There was increased risk of malignancy in the CYC-treated group, with 50 cancers found in 37 patients in the CYC group compared with 26 cancers in 25 of the control patients (P < 0.05). The relative risk of cancer for those treated with CYC was 1.5 (95% confidence interval 0.93-5.5). Nine of the malignancies in the CYC group were bladder cancers and 19 were skin cancers, compared with no bladder cancers and 6 skin cancers in the control group. The total dose of CYC was higher in those who developed cancer, particularly in those with bladder cancer. Three of the bladder cancers occurred 14, 16, and 17 years after CYC had been discontinued.
  
  
  CONCLUSIONS
  The risk of malignancy, particularly bladder cancer, in RA patients treated with oral CYC continues even 17 years after discontinuation of the drug.
authors.affiliation: University of Pittsburgh School of Medicine, Pennsylvania, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Radis
authors.forename: L E
authors.initials: LE
authors.lastname: Kahl
authors.forename: G L
authors.initials: GL
authors.lastname: Baker
authors.forename: M C
authors.initials: MC
authors.lastname: Wasko
authors.forename: J M
authors.initials: JM
authors.lastname: Cash
authors.forename: A
authors.initials: A
authors.lastname: Gallatin
authors.forename: B L
authors.initials: BL
authors.lastname: Stolzer
authors.forename: A K
authors.initials: AK
authors.lastname: Agarwal
authors.forename: T A
authors.initials: TA
authors.lastname: Medsger
authors.forename: C K
authors.initials: CK
authors.lastname: Kwoh
mesh_terms: D000367:Age Factors; D001161:Arteriosclerosis / Q000150:complications / Q000453:epidemiology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000150:complications / Q000453:epidemiology; D009369:Neoplasms / Q000139:chemically induced* / Q000150:complications; D012307:Risk Factors; D012878:Skin Neoplasms / Q000150:complications / Q000453:epidemiology; D016019:Survival Analysis; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000150:complications / Q000453:epidemiology
chemical_list: D003520:Cyclophosphamide