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Evaluation of Alternate Size Descriptors for Dose Calculation of Anticancer Drugs in the Obese

Alex Sparreboom, Antonio C. Wolff, Ron H.J. Mathijssen, Etienne Chatelut, Eric K. Rowinsky, Jaap Verweij, Sharyn D. Baker

From the Department of Medical Oncology, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Institut Claudius-Regaud, Toulouse, France; and the Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX

Address reprint requests to Alex Sparreboom, PhD, Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, 332 North Lauderdale, DTRC, Mail Stop 314, Room D1034B, Memphis, TN 38105; e-mail: alex.sparreboom{at}stjude.org

Purpose Despite the rising prevalence of obesity, there is paucity of information describing how doses of anticancer drugs should be adjusted in clinical practice. Here, we assessed the pharmacokinetics of eight anticancer drugs in adults and evaluated the potential utility of alternative weight descriptors in dose calculation for the obese.

Patients and Methods A total of 1,206 adult cancer patients were studied, of whom 162 (13.4%) were obese (body mass index 30). Pharmacokinetic parameters were calculated using noncompartmental analysis, and compared between lean (body mass index 25) and obese patients.

Results The absolute clearance of cisplatin, paclitaxel, and troxacitabine was significantly increased in the obese (P < .023), but this was not observed for carboplatin, docetaxel, irinotecan, or topotecan (P < .17). For doxorubicin, the systemic clearance was statistically significantly reduced in obese women (P = .013), but not in obese men (P = .52). Evaluation of alternate weight descriptors for dose calculation in the obese, including predicted normal weight, lean body mass, (adjusted) ideal body weight, and the mean of ideal and actual body weight, indicated that, for most of the evaluated drugs, weight scalars used to calculate body-surface area should consider actual body weight regardless of size.

Conclusion The results suggest that a number of widely used empiric strategies for dose adjustments in obese patients, including a priori dose reduction or dose capping, should be discouraged.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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