Capecitabine (cape) is a pro-drug for the cytotoxic agent 5-fluorouracil and widely used in the treatment of colorectal cancer. In general, cape is dosed on body surface area (BSA), despite all drawbacks of this dosing strategy. In this study, toxicity and efficacy of flat-dosed cape (i.e. without adjustments for body size) was analysed, and compared to BSA-dosed cape.
All patients treated with cape at our center between 2003-2015 were included when they had been treated with flat-dosed cape and no prior treatment with fluoropyrimidines. Data on adverse events and survival was collected. Cape-specific toxicity (CStox) was defined as toxicity grade for diarrhea ≥ 3, hand-foot syndrome ≥ 2 and neutropenia ≥ 2. Clinical relevant toxicity (CRtox) consisted of hospital admission, dose delay, reduction or discontinuation. Patients were divided per treatment in 3 groups based on BSA-quartiles: lowest 25%, middle 50% and highest 25%, corrected for sex. Toxicity was compared using the X2-test and binary logistic regression analysis. Survival analysis was done by the Kaplan-Meier method.
Among 1952 evaluated patients; 1055 patients were included (60% male). Three regimes were evaluated: cape-radiotherapy (CRT, n = 769), cape-oxaliplatin (CAPOX, n = 189) and cape monotherapy (MONO, n = 97). The mean dose of flat-dosed cape was 7.1% lower compared to BSA-dosed cape (p 0.05), for CRT there was a difference in CStox (p = 0.009) and CRtox (p = 0.014). Corrected for sex, age and renal function, only in the CRT group BSA predicted CStox (OR: 0.248, 95% CI: 0.072-0.857, p = 0.028) and CRtox (OR: 0.246, 95% CI: 0.083-0.727, p = 0.011). Survival analyses for CAPOX and CRT showed no differences between BSA-groups and median survival was comparable to literature.
Flat-dosed cape is safe in CAPOX and MONO. Only in CRT, BSA is predictive for CStox and CRtox. No survival differences could be identified in subgroups. Therefore, flat-dosed cape is a safe and effective dosing strategy in regimens without RT.
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Department of Medical Oncology, Erasmus MC Cancer Institute
All authors have declared no conflicts of interest.