TY - JOUR
T1 - Dose calculation of anticancer drugs
AU - Gao, Bo
AU - Klumpen, Heinz Josef
AU - Gurney, Howard
PY - 2008/10
Y1 - 2008/10
N2 - 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 underclosing 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.
AB - 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 underclosing 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.
UR - http://www.scopus.com/inward/record.url?scp=55049115153&partnerID=8YFLogxK
U2 - 10.1517/17425255.4.10.1307
DO - 10.1517/17425255.4.10.1307
M3 - Review article
C2 - 18798700
AN - SCOPUS:55049115153
SN - 1742-5255
VL - 4
SP - 1307
EP - 1319
JO - Expert Opinion on Drug Metabolism and Toxicology
JF - Expert Opinion on Drug Metabolism and Toxicology
IS - 10
ER -