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Journal of Clinical Oncology, Vol 20, Issue 1 (January), 2002: 81-87
© 2002 American Society for Clinical Oncology

Impact of Body-Size Measures on Irinotecan Clearance: Alternative Dosing Recommendations

By Ron H.J. Mathijssen, Jaap Verweij, Maja J.A. de Jonge, Kees Nooter, Gerrit Stoter, Alex Sparreboom

From the Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, Rotterdam, the Netherlands.

Address reprint requests to Alex Sparreboom, PhD, Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, PO Box 5201, 3008 AE Rotterdam, the Netherlands; email: sparreboom{at}onch.azr.nl

PURPOSE: To evaluate relationships between various body-size measures and irinotecan (CPT-11) clearance and metabolism in cancer patients, and to provide future dosing recommendations for this agent.

PATIENTS AND METHODS: Pharmacokinetic data were obtained from 82 adult patients (50 men, 32 women; median age, 54 years) receiving CPT-11 as a 90-minute intravenous infusion (dose range, 175 to 350 mg/m2). In each patient, plasma samples were collected at timed intervals in the first administration of a 3-week schedule, and CPT-11 and its metabolite, SN-38, were measured by a liquid chromatographic assay.

RESULTS: The mean (± SD) CPT-11 clearance was 33.6 ± 10.8 L/h, with an interindividual variability (IIV) of 32.1%. When clearance was adjusted for body-surface area (BSA), the IIV was similar (34.0%). In addition, in a multiple linear regression analysis, none of the studied measures (BSA, lean body mass, [adjusted] ideal body weight, and body mass index) was a significant covariate (P > .13; r2 < .014) in our population. Similarly, BSA did not significantly contribute to variability in the relative extent of conversion to SN-38 (P = .26).

CONCLUSION: BSA is not a predictor of CPT-11 clearance or SN-38 pharmacokinetics and does not contribute to reducing kinetic variability. These findings provide a rationale for the conduct of a comparative phase III study between BSA-based dosing and flat or fixed dosing of CPT-11.


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