title: Differences in toxicity between men and women treated with 5-fluorouracil therapy for colorectal carcinoma.
abstract: BACKGROUND
  Recent explorations suggest that women may experience more severe 5-fluorouracil (5-FU)-related toxicity than men. The patient populations from 4 Southwest Oncology Group colorectal carcinoma trials with 5-FU-containing regimens were examined for toxicity differences between the genders.
  
  
  METHODS
  The current study included 1074 patients from 4 trials. Hypotheses regarding differences in specific toxicities were generated via exploratory analyses on the data from the 2 earlier trials (n = 505 patients), using basic univariate techniques and classification tree methods. Validation of these hypotheses was performed on data from the 2 later trials (n = 569 patients) using logistic regression models for dichotomous toxicity outcomes and rank-sum tests for comparisons of overall toxicity grade.
  
  
  RESULTS
  5-FU toxicity was more extensive in women than in men in terms of average maximum toxicity grade (P = 0.005), number of different types of toxicity experienced (P = 0.009), and incidence of severe toxicities (P = 0.02). The incidence of > or = Grade 2 hematologic toxicity in the 2 later trials was higher in women than in men and women experienced more frequent moderate to severe mucositis compared with men.
  
  
  CONCLUSIONS
  Differences in 5-FU toxicity profiles between men and women were hypothesized after an exploratory analysis, and then verified by an independent confirmatory analysis using data from the 2 later trials. This process provided substantial evidence for gender differences in specific aspects of 5-FU toxicity that persist across a range of treatment regimens, patient characteristics, and cancer trial settings.
authors.affiliation: Southwest Oncology Group Statistical Center, Seattle, Washington, USA.
authors.forename: Kari
authors.initials: K
authors.lastname: Chansky
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Benedetti
authors.forename: John S
authors.initials: JS
authors.lastname: Macdonald
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D017024:Chemotherapy, Adjuvant; D003082:Colectomy / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018570:Risk Assessment; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005472:Fluorouracil