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JNCI Journal of the National Cancer Institute 1999 91(23):1983-1985; doi:10.1093/jnci/91.23.1983
© 1999 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 91, No. 23, 1983-1985, December 1, 1999
© 1999 Oxford University Press

EDITORIALS

Application of Pharmacogenetics to Optimization of Mercaptopurine Dosing

Frank M. Balis, Peter C. Adamson

Affiliations of authors: F. M. Balis, Pediatric Oncology Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD; P. C. Adamson, Division of Clinical Pharmacology and Therapeutics, Children's Hospital of Philadelphia, PA.

Correspondence to: Frank M. Balis, M.D., National Institutes of Health, Bldg. 10, Rm. 13N240, Bethesda, MD 20892-1928.

The traditional approach to dosing anticancer drugs is to administer a standard starting dose, which is normalized to body surface area, and then to adjust or individualize subsequent doses based on the severity of ensuing drug toxicity. Dosing according to body surface area is based on the assumption that the volume of distribution and drug elimination mechanisms are proportional to the body surface area. However, pharmacokinetic studies of anticancer drugs typically reveal substantial interpatient variability in plasma drug concentrations when the dose is based on body surface area (1). The potential consequences of this variability in systemic drug exposure are life-threatening toxic effects in patients who are exposed to overly toxic drug concentrations and tumor progression in patients who achieve subtherapeutic drug concentrations. The identification of specific factors that account for variability in drug disposition among patients can . . . [Full Text of this Article]

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