Sex differences in fluorouracil-induced stomatitis.
OBJECTIVE
A meta-analysis of six North Central Cancer Treatment Group (NCCTG) trials involving patients receiving their first ever fluorouracil (5-FU)-based chemotherapy was undertaken to explore the association of sex with reports of the incidence and severity of stomatitis.


METHODS
Data were obtained on a total of 731 patients (402 men and 329 women). Comparisons of incidence and severity rates and average stomatitis across sex were performed using standard binomial testing and t tests, respectively. Logistic regression analysis and a weighted analysis using data summarized to study level served as evidence of cross-validation.


RESULTS
Women reported stomatitis both more often and with greater severity than did men. The incidence of any stomatitis for women was 63% versus 52% for men (P =.002). The incidence of severe or very severe stomatitis for men and women was 22% and 12%, respectively (P =. 0006). On average, women reported stomatitis of roughly 0.4 points higher than men on a 0 to 4 ordinal scale (P <.00001). Comparison of results across treatment and placebo arms was carried out to validate the initial findings. Logistic regression modelling further confirmed the results conditional on the presence of a number of potentially confounding covariates. Women were also 11% more likely than men to experience leukopenia of common toxicity criteria grade >/= 1, (70% v 59%, respectively; P <.00001) and grade 3+ (18% v 11%, respectively; P =.004).


CONCLUSIONS
More women than men reported 5-FU-induced stomatitis. The precise mechanism resulting in different degrees of stomatitis across sex is not evident.
Sloan
J A
JA
Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. jsloan@mayo.edu
Loprinzi
C L
CL
Novotny
P J
PJ
Okuno
S
S
Nair
S
S
Barton
D L
DL
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D013280:Stomatitis / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil