Colorectal cancer chemotherapy: can sex-specific disparities impact on drug toxicities?

Eur J Clin Pharmacol. 2022 Jun;78(6):1029-1038. doi: 10.1007/s00228-022-03298-y. Epub 2022 Feb 22.

Abstract

Purpose: Given the biological differences between females and males, sex-specific evaluations should be carried out to obtain better cancer prevention, diagnosis, and treatment strategies. To this purpose, our aim was to evaluate sex differences for toxicity in a cohort of colorectal cancer (CRC) patients undergoing chemotherapy.

Methods: We performed a retrospective study in 329 CRC patients. Differences between males and females were tested performing the Mann-Whitney U test or the Fisher exact test. Multivariate logistic regression models were computed to evaluate the association between sex and risk of chemotherapy agent-related toxicity.

Results: According association sex toxicity, significant differences were observed in the median number of episodes of nausea (p = 0.044), vomit (p = 0.007), heartburn (p = 0.022), thrombocytopenia (p = 0.005), mucositis (p = 0.024). Moreover, statistically significant differences between males and females were observed in the distribution of the highest toxicity grades of nausea (p = 0.024), heartburn (p = 0.016), and thrombocytopenia (p = 0.034). Females have an increased risk of vomit (p = 0.002), alopecia (p = 0.035), heartburn (p = 0.005), mucositis (p = 0.003), and lower risk for thrombocytopenia (p = 0.005).

Conclusion: According to the association of sex chemotherapy agent-related toxicities, females resulted on average at a significant increased risk of more common adverse events (constipation, dysgeusia, alopecia, heartburn, vomit, asthenia, nausea, pain events, and mucositis). Sex-tailored CRC chemotherapy treatment is necessary to obtain efficacy avoiding toxicity, based on patients' biological and genetic characteristics, a vision that would change CRC setting, a stable disease but still orphan of a real tailored approach.

Keywords: Adverse events; Chemotherapy; Colorectal cancer; Personalized medicine; Sex.

MeSH terms

  • Alopecia / chemically induced
  • Anemia* / drug therapy
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Drug-Related Side Effects and Adverse Reactions* / epidemiology
  • Drug-Related Side Effects and Adverse Reactions* / etiology
  • Female
  • Fluorouracil / therapeutic use
  • Heartburn / chemically induced
  • Heartburn / drug therapy
  • Humans
  • Leucovorin
  • Male
  • Mucositis* / chemically induced
  • Mucositis* / epidemiology
  • Nausea / chemically induced
  • Nausea / drug therapy
  • Nausea / epidemiology
  • Retrospective Studies
  • Thrombocytopenia* / chemically induced
  • Thrombocytopenia* / drug therapy
  • Vomiting / chemically induced

Substances

  • Leucovorin
  • Fluorouracil