Sex differences in toxicities and survival outcomes among Japanese patients with Stage III colorectal cancer receiving adjuvant fluoropyrimidine monotherapy: A pooled analysis of 4 randomized controlled trials (JCOG2310A)

Abstract

Background: Fluoropyrimidine remains the key agent of adjuvant chemotherapy for stage III colorectal cancer (CRC). Western studies have shown that female sex is a favorable prognostic factor after surgery, but it is also a risk factor for adverse events (AEs) during adjuvant chemotherapy with fluoropyrimidine. However, little is known about whether sex differences in treatment outcomes exist in this setting in the Asian population.

Methods: Patients with stage III CRC who received adjuvant fluoropyrimidine monotherapy in 4 randomized controlled trials were analyzed. Incidences of AEs and survival outcomes were compared between female and male patients.

Results: A total of 3170 patients (female, 1516; male, 1654) were included in this analysis. Compared with males, females were less likely to have a relative dose intensity (≥90 %: female 59.1 % vs. male 67.6 %), with a higher proportion of requiring dose reduction (28.8 % vs. 20.4 %) and a lower proportion of completing adjuvant chemotherapy (77.0 % vs. 81.7 %). Multivariable analyses demonstrated that female sex was associated with a higher incidence of grade 3-4 AEs (odds ratio 1.80 [95 % CI 1.51-2.14]). Female sex was identified as a favorable prognostic factor for overall survival (hazard ratio [HR]: 0.80 [0.65-0.97]) and relapse-free survival (HR: 0.73 [0.63-0.85]) in multivariable analyses. Female patients had fewer time-to recurrence (TTR) events than male patients (5-year TTR: 17.7 % vs. 22.3 %).

Conclusion: Sex had implications for the development of AEs and survival outcomes of Japanese patients with stage III CRC who received adjuvant fluoropyrimidine monotherapy.

Keywords: Adjuvant chemotherapy; Colorectal cancer; Fluoropyrimidine; Sex difference.