Effects of gender on capecitabine toxicity in colorectal cancer. (June 2016)

• Record Type: Journal Article
• Authors: Ilich, Alastair I; Danilak, Melanie; Kim, Christina A; Mulder, Karen E; Spratlin, Jennifer L; Ghosh, Sunita; Chambers, Carole R; Sawyer, Michael B
• Is Part Of: Journal of oncology pharmacy practice. Volume 22:Number 3(2016:Sep.)
• Page Start: 454
• Page End: 460
• Publication Date: 2016-06
• Subjects: Capecitabine -- dosing -- gender -- pharmacokinetics -- toxicity -- colorectal; Cancer -- Chemotherapy -- Periodicals; Clinical pharmacology -- Periodicals; 616.994061
• DOI: 10.1177/1078155215587345
• Languages: English
• ISSNs: 1078-1552

Abstract

Background: Capecitabine is a highly water soluble prodrug of 5-fluorouracil that is dosed by patient body surface area. Body surface area dosing makes no allowances for differences in body composition. There is mounting evidence that lean body mass is a better predictor of toxicity than body surface area for drugs which distribute into the lean compartment. Because women, on average, have lower lean body mass than men, we expect that women would experience a higher incidence of toxicity than men when body surface area dosing is used. Objective: To determine whether female colorectal cancer patients experienced a higher incidence of dose-limiting toxicity than men when treated with adjuvant capecitabine. Methods: We conducted a retrospective chart review of colorectal cancer patients treated with adjuvant capecitabine at our institute between 2008 and 2012. Patients receiving capecitabine were identified from the pharmacy dispensing database and then screened for inclusion. Dosing and toxicity information were gathered and dose-limiting toxicity incidence (defined as a composite endpoint of dose delay, dose reduction, or discontinuation of therapy) was compared between males and females using the chi-square test. Binary logistic regression analysis was then performed to account for differences between male and female populations. Results: A total of 299 patients (163 males, 136 females) met inclusion criteria. Females had a significantly higher dose-limiting toxicity incidence than males (67.7 vs. 52.2%, p = 0.007). Relationships between gender and dose-limiting toxicity incidence remained significant after logistic regression analysis (OR: 2.04; 95% CI: 1.23–3.36). Conclusion: Female colorectal cancer patients experience a higher dose-limiting toxicity incidence than male patients when given adjuvant capecitabine dosed according to body surface area.