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Women Experience Greater Toxicity With Fluorouracil-Based Chemotherapy for Colorectal Cancer

From the Mayo Clinic and Mayo Foundation, Rochester, MN; Geisinger Clinic & Medical Center Community Clinical Oncology Program, Danville, PA; and Saskatchewan Cancer Foundation, Allan Blair Memorial Center, Regina, Saskatchewan, Canada.

Address reprint requests to Jeff Sloan, PhD, Mayo Clinic, 200 First St, SW, Rochester, MN 55905; email: jsloan{at}mayo.edu

PURPOSE: The toxicity profile of fluorouracil (5-FU)–based chemotherapy given on 5 consecutive days at doses of 370 to 450 mg/m² has been well documented. A meta-analysis of six North Central Cancer Treatment Group (NCCTG) cancer control trials involving 786 patients indicated that women treated with this type of regimen experienced more severe stomatitis and leukopenia than men. After these findings, an additional meta-analysis of the toxicity profiles on five NCCTG colorectal cancer treatment trials was undertaken.

METHODS: Data for 1,093 women and 1,355 men from 12 different treatment arms were included. The primary end points were the incidence of stomatitis, leukopenia, alopecia, diarrhea, nausea, and vomiting, recorded with standard National Cancer Institute common toxicity criteria. Fisher’s exact test was used to compare incidence and severity across sexes, supplemented by Forrest meta-analysis plots and logistic regression.

RESULTS: The incidence of four out of six toxicities studied was significantly greater for women than men; the exceptions were severe nausea and vomiting. Overall, almost half of the women compared with a third of the men experienced severe toxicity (P < .0001). Logistic regression confirmed the univariate findings while adjusting for the effects of study, dose, body mass index, and age. The differences were consistent across treatment cycles. Response rates and survival distributions were the same for both sexes.

CONCLUSION: This study confirms an earlier finding that women receiving 5-FU–based chemotherapy in a 5-day bolus schedule experience toxicity more frequently and with more severity than men. These data raise the question of whether the recommended initial dose of 5-FU–based chemotherapy for women should be lower than that for men.

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