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Clinical Pharmacology

Flat-Fixed Dosing Versus Body Surface Area–Based Dosing of Anticancer Drugs in Adults: Does It Make a Difference?

Department of Medical Oncology, Erasmus University Medical Center Rotterdam – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

Key Words. BSA • Flat-fixed dosing • Pharmacokinetics • Pharmacodynamics • Individualized dosing

Correspondence: Ron H.J. Mathijssen, M.D., Ph.D., Erasmus University Medical Center Rotterdam – Daniel den Hoed Cancer Center, Department of Medical Oncology, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands. Telephone: 31-10-4391-112; Fax: 31-10-4391-053; e-mail: a.mathijssen{at}erasmusmc.nl

Received November 14, 2006; accepted for publication February 12, 2007.

The current practice of using body-surface area (BSA) in dosing anticancer agents was implemented in clinical oncology half a century ago. By correcting for BSA, it was generally assumed that cancer patients would receive a dose of a particular cytotoxic drug associated with an acceptable degree of toxicities without reducing the agent's therapeutic effect. More recently, doubt has arisen to this hypothesis, and for many drugs, the effects of BSA on the pharmacokinetics of these agents have therefore been studied retrospectively. In (by far) most cases, use of BSA does not reduce the interindividual variation in the pharmacokinetics of adults, and thus, a logical rationale for further use of this tool in dosing adults is lacking. As a result, alternative dosing strategies have been proposed in order to replace BSA-based dosing. Flat-fixed dosing regimens have been suggested, thereby avoiding potential dose calculation mistakes. As flat-fixed dosing does not typically lead to greater pharmacokinetic variability, it does not seem worse than using BSA-based dosing. While it provides a simplification, it can, however, be questioned whether to call this an improvement or not. The implementation of so-called genotyping and phenotyping strategies, and therapeutic drug monitoring, may probably be of more clinical value. In the end, the nonscientifically based BSA-based dosing strategy should be replaced by alternative strategies. Despite the lack of basic fundamentals, BSA-based dosing still seems "untouchable" in clinical oncology. Even when alternatives will be shown to be indisputably better, many hurdles will probably have to be overcome before physicians will be willing to ban BSA-based dosing.

Disclosure of potential conflicts of interest is found at the end of this article.

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