Dose calculation of anticancer drugs

Abstract

Background: Anticancer drugs are characterized by a narrow therapeutic window and significant inter-patient variability in therapeutic and toxic effects. Current body surface area (BSA)-based dosing fails to standardize systemic anticancer drug exposure and other alternative dosing strategies also have their limitations. Just as important as the initial dose selection is the subsequent dose revision to ensure the dose is correct. Objective: To provide an insight into the different dose individualization and dose adjustment methods, their feasibility and applicability in daily oncology practice and to suggest a practical framework for dose calculation and a basis for future research. Methods: Review of relevant literature related to dose calculation of anticancer drugs. Results: Strategies using clinical parameters, genotype and phenotype markers, and therapeutic drug monitoring all have potential and each has a role for specific drugs. However, no one method is a practical dose calculation strategy for many or all drugs. Conclusion: Given that BSA-dosing leads to significant underdosing it is not reasonable to use this as the sole method of dose calculation. Because of wide disparity in individual patient characteristics and elimination mechanisms, we are unlikely to find the ‘Holy Grail’ of a single individualized dosing strategy for every patient and anticancer drug in the near future. We propose a pragmatic, although invalidated system for initial dose calculation using dose clusters and structured subsequent dose revision based on treatment-related toxicities and therapeutic drug monitoring. These models need to be tested in clinical trials.