Comparison of toxicity and effectiveness between fixed-dose and body surface area-based dose capecitabine
Background: Capecitabine is generally dosed based on body surface area (BSA). This dosing strategy has several limitations; however, evidence for alternative strategies is lacking. Therefore, we analyzed the toxicity and effectiveness of fixed-dose capecitabine and compared this strategy with a BSA-based dose of capecitabine in a large set of patients.
Methods: Patients treated with fixed-dose capecitabine between 2003 and 2015 were studied. A comparable group of patients, dosed based on BSA, was chosen as a control cohort. A total of two combined scores were used: capecitabine-specific toxicity (diarrhea, National Cancer Institute Common Toxicity Criteria grade ⩾3, hand-foot syndrome ⩾2, or neutropenia ⩾2), and clinically relevant events due to toxicity, that is, hospital admission, dose reduction, or discontinuation. Per treatment regimen, patients were divided into three BSA groups based on BSA quartiles corrected for sex. Toxicity scores were compared by a Chi-square test between cohorts, and within cohorts using BSA groups. Progression-free survival (PFS) was estimated by the Kaplan–Meier method.
Results: A total of 2319 patients were included (fixed dosed, n = 1126 and BSA-based dose, n = 1193). Overall, four regimens were evaluated: capecitabine-radiotherapy (n = 1178), capecitabine-oxaliplatin (n = 519), capecitabine triplet (n = 181) and capecitabine monotherapy (n = 441). The incidence of capecitabine-specific toxicity and clinically relevant events was comparable between fixed-dose and BSA-dosed patients, while a small difference (7.1%) in absolute dose was found. Both cohorts showed only a higher incidence of both toxicity scores in the lowest BSA group of the capecitabine-radiotherapy group (p < 0.05). Subgroups of the fixed-dose cohort analyzed for PFS, showed no differences between BSA groups.
Conclusions: Fixed-dose capecitabine is as comparably well tolerated and effective as BSA-based dosing and could be considered as a reasonable alternative for BSA-based dosing.
|Keywords||BSA, capecitabine, fixed-dose, survival, toxicity|
|Persistent URL||dx.doi.org/10.1177/1758835919838964, hdl.handle.net/1765/118935|
|Journal||Therapeutic Advances in Medical Oncology|
de Man, F.M., Veerman, GDM, Oomen - de Hoop, E, Deenen, M.J, Meulendijks, D., Mandigers, C, … Mathijssen, A.H.J. (2019). Comparison of toxicity and effectiveness between fixed-dose and body surface area-based dose capecitabine. Therapeutic Advances in Medical Oncology, 11. doi:10.1177/1758835919838964