Dose calculation of anticancer drugs.
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.


CONCLUSIONS
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.
Gao
Bo
B
Westmead Hospital Sydney West Area Health Service, Department of Medical Oncology, Westmead, NSW 2145, Australia.
Klumpen
Heinz-Josef
HJ
Gurney
Howard
H
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001830:Body Surface Area; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005838:Genotype; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010641:Phenotype
D000970:Antineoplastic Agents