© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 24, 1883-1888,
December 18, 2002
© 2002 Oxford University Press
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Role of Body Surface Area in Dosing of Investigational Anticancer Agents in Adults, 1991–2001
Affiliations of authors: S. D. Baker, R. C. Donehower, L. B. Grochow, Division of Experimental Therapeutics, The Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; J. Verweij, J. H. M. Schellens, A. Sparreboom, Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands; E. K. Rowinsky, The Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX.
Correspondence to: Sharyn D. Baker, Pharm.D., Division of Experimental Therapeutics, The Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans St., Rm. 1M87, Baltimore, MD 21237 (e-mail: sdbaker{at}jhmi.edu).
ABSTRACT
The prescribed dose of anticancer agents is most commonly calculated using body surface area as the only independent variable, and it has been shown that this approach still results in large interpatient variability in drug exposure. Here, we retrospectively assessed the pharmacokinetics of 33 investigational agents tested in phase I trials from 1991 through 2001, as a function of body surface area in 1650 adult cancer patients. Twelve of the drugs were administered orally, 19 were administered intravenously, and two were administered by both routes. Body surface area-based dosing was statistically significantly associated with a reduction in interpatient variability in drug clearance for only five of the 33 agents: docosahexaenoic acid (DHA)–paclitaxel, 5-fluorouracil/eniluracil, paclitaxel, temozolomide, and troxacitabine. These results do not support the use of body surface area in dose calculations and suggest that alternate dosing strategies should be evaluated. We conclude that body surface area should not be used to determine starting doses of investigational agents in future phase I studies.
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- Re: Role of Body Surface Area in Dosing of Investigational Anticancer Agents in Adults, 1991-2001
- Yuichi Ando, Tomoko Ohtsu, Masahiko Ando, Fumiyoshi Ohyanagi, Fumio Nagashima, Masaru Narabayashi, Nagahiro Saijo, and Yasutsuna Sasaki
J Natl Cancer Inst 2003 95: 1638-1640.[Extract] [Full Text] [PDF]
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