Effects of gender on capecitabine toxicity in colorectal cancer.

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.

Concomitant Administration of Proton Pump Inhibitors and Capecitabine is Associated With Increased Recurrence Risk in Early Stage Colorectal Cancer Patients.

BACKGROUND: Capecitabine is used to treat colorectal (CRC) cancer. TRIO-013, a study examining capecitabine/oxaliplatin ± lapatinib in metastatic gastro-esophageal cancer did not show increases in overall survival (OS) with lapatinib. An analysis showed concurrent proton pump inhibitor (PPI) usage negatively impacted recurrence-free survival (RFS). We retrospectively studied PPI effects on capecitabine efficacy in early stage CRC and how capecitabine adjustments impacted RFS. METHODS: Early stage CRC patients taking monotherapy capecitabine treated from 2008 to 2012 were reviewed for demographics, medications, toxicities, and patient outcomes. RESULTS: Of 298 identified patients, 25.8% (n = 77) received concurrent PPIs. Five-year RFS was 74% versus 83% (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.07-3.35; P = .03) in PPI versus non-PPI patients respectively. OS was 81% versus 78%, respectively (HR, 1.13; 95% CI, 0.60-2.14; P = .7). After accounting for gender, stage, age, and performance status, PPI patients tended toward decreased RFS (HR, 1.65; 95% CI, 0.93-2.94; P = .09). Capecitabine dose modifications affected outcomes. Five-year RFS was 84% in the control group, 100% in the treatment-delay group (P = .99), 67% in the dose reduction group (HR, 2.46; 95% CI, 1.23-4.93; P = .01), and 64% in the discontinuation group (HR, 2.27; 95% CI, 0.93-5.53; P = .07). Five-year OS was significantly less in the discontinuation group than control group (59% vs. 82%; HR, 3.27; 95% CI, 1.44-7.45; P = .005). CONCLUSIONS: PPIs appear to impact RFS; this may be due to PPIs preventing capecitabine tablet dissolution and absorption. Patients with dose reductions or who stopped treatment had worse outcomes than patients who continued with treatment at starting doses.