Sex differences in chemotherapy completion, toxicities, and survival in colon cancer: an analysis of 2201 patients from CALGB/SWOG 80702 (alliance)

Abstract Background Completing adjuvant chemotherapy and reducing toxicities are critical tenets to maximize survival after colon cancer diagnosis. Sex, as a biological variable, may impact colon cancer chemotherapy completion, toxicities, and survival differently. Methods From an NCI-sponsored trial conducted among patients with stage III colon cancer (CALGB/SWOG 80702), we included 2201 patients receiving standard adjuvant chemotherapy FOLFOX (fluorouracil, leucovorin, and oxaliplatin). We calculated relative dose intensity (RDI) to indicate chemotherapy completion and considered reduced RDI (RDI <85%) as a clinically significant deviation from standard FOLFOX. Using NCI’s Common Terminology Criteria for Adverse Events (AE), we defined severe AE (grade ≥3) as the occurrence of any following event including neutrophils decrease, nausea, platelets decrease, hypertension, peripheral neuropathy, diarrhea, fatigue, gastritis, creatinine increase, gastric ulcer, myocardial ischemia, and cerebral ischemia. The primary survival outcome was disease-free survival (time from enrollment to colon cancer recurrence or death from any cause), and secondary survival outcomes were recurrence-free and overall survival. Results Compared to males, females were at significantly higher risks of experiencing reduced RDI (adjusted OR 1.59 [1.29-1.96]; P < .001) and severe AE (adjusted OR: 1.72 [1.41-2.11]; P < .001). Yet, females had significantly better disease-free survival (adjusted HR: 0.72 [0.59, 0.87]; P < .001) as well as better recurrence-free and overall survival. Conclusions Our findings suggested that females with colon cancer are more likely to have worse chemotherapy completion and more severe AE, but they have better survival. Sex, as a biological variable, warrants further consideration in chemotherapy administration and survivorship management after colon cancer diagnosis.