Purpose: To evaluate the impact of sex on toxicity and efficacy outcomes among patients with metastatic colorectal cancer receiving first-line 5-fluorouracil-based regimens.
Patients and methods: A pooled analysis of data sets from 5 clinical trials (NCT00115765, NCT00364013, NCT00272051, NCT00305188, NCT00384176) was performed. Kaplan-Meier analysis and log-rank testing were used to assess the differences in overall and progression-free survival between male and female subjects. Chi-square testing was used to examine the differences in the incidence of different toxicities between male and female subjects. Multivariate logistic regression analysis (adjusted for age, body mass index, Eastern Cooperative Oncology Group performance status, race, bevacizumab-containing treatment, and panitumumab-containing treatment) was further utilized to assess the impact of gender on different toxicities. Most of the patients were treated with FOLFOX (folinic acid, fluorouracil, and oxaliplatin)-based regimens.
Results: A total of 3223 participants were included in the pooled cohort, among which were 1925 male and 1298 female subjects. Kaplan-Meier survival analysis and log-rank testing were utilized to compare overall and progression-free survival outcomes between male and female subjects. For both end points, there was no difference between male and female subjects (P = .884; P = .647, respectively). Comparing female to male subjects, female subjects were more likely to experience alopecia (20% vs. 8.6%; P < .001), all-grade diarrhea (60.3% vs. 56.7%; P = .039), all-grade nausea and vomiting (68.7% vs. 56.6%; P < .001), high-grade nausea and vomiting (7.1% vs. 4.5%; P = .002), all-grade anemia (19.6% vs. 14.2%; P < .001), all-grade neutropenia (51.1% vs. 36.6%; P < .001), and high-grade neutropenia (37.1% vs. 24.1%; P < .001). These differences were further confirmed in multivariate logistic regression analyses.
Conclusion: Female subjects with metastatic colorectal cancer receiving first-line chemotherapy demonstrated higher rates of a number of toxicities (essentially hematologic and gastrointestinal in nature). Additional studies into the differential effect of systemic therapy on female versus male subjects are needed.
Keywords: 5-FU; Adverse events; Female; Male; Survival.
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