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Evaluation of an Alternate Dosing Strategy for Cisplatin in Patients With Extreme Body Surface Area Values

Walter J. Loos, Felix E. de Jongh, Alex Sparreboom, Ronald de Wit, Desiree M. van Boven-van Zomeren, Gerrit Stoter, Kees Nooter, Jaap Verweij

From the Department of Medical Oncology, Erasmus MC, Daniel den Hoed Cancer Center, Rotterdam, the Netherlands

Address reprint requests to Walter J. Loos, PhD, Department of Medical Oncology, Erasmus MC, Daniel den Hoed Cancer Center, PO Box 5201, 3008 AE Rotterdam, the Netherlands; e-mail: w.loos{at}erasmusmc.nl

PURPOSE: The majority of cytotoxic drugs for adults are dosed based on body surface area (BSA), aiming to reduce interpatient variability in drug exposure. We prospectively studied the usefulness of BSA-based dosing of cisplatin in patients at extremes of BSA values.

PATIENTS AND METHODS: Patients were randomly assigned to receive a fixed dose of cisplatin in course 1, and a BSA-adjusted dose in course 2, or vice versa. The fixed dose was based on the average BSA for males and females, while extremes were set at BSA values exceeding the average ± 1 standard deviation. Subsequently, we retrospectively analyzed data from a normal population.

RESULTS: In 25 patients assessable for both courses, the use of a fixed dose of cisplatin resulted in reduced exposure to unbound platinum in patients at the upper extremes of BSA (P = .003) and higher exposures in patients at the lower extremes (P = .009), as compared with exposures following the BSA-adjusted dose. Although clearance was related to BSA (R² = 0.44; P < .001), only a small reduction in interpatient variability in clearance after correction for BSA was achieved (20.8% v 17.1%). In the retrospective analysis, compared with the average patient, the clearance of unbound platinum in patients with a BSA value 1.65 m² was 16% slower (P < .001), while an 18% faster clearance (P < .001) was observed in patients with a BSA value 2.05 m².

CONCLUSION: Unless better predictors for platinum clearance are identified, fixed-dose regimens per BSA cluster ( 1.65 m²; 1.66 m² to 2.04 m²; 2.05 m²) are recommended.

Presented in part at the Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, Orlando, FL, March 2-6, 2005.

F.E.J. is currently with the Department of Internal Medicine, Ikazia Hospital, Rotterdam, the Netherlands, and A.S. is currently with the National Cancer Institute, Bethesda, MD.

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

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