• 5-fluorouracil;
  • colorectal carcinoma;
  • toxicity;
  • gender;
  • classification trees;
  • clinical trials



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.


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.


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 ≥ 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.


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. Cancer 2005. © 2005 American Cancer Society.