Body-surface area-based dosing does not increase accuracy of predicting cisplatin exposure
In: Journal of clinical oncology, Jg. 19 (2001), Heft 17, S. 3733-3739
Online
academicJournal
- print, 28 ref
Zugriff:
Purpose: Most anticancer drugs are dosed based on body-surface area (BSA) to reduce interindividual variability of drug effects. We evaluated the relevance of this concept for cisplatin by analyzing cisplatin pharmacokinetics obtained in prospective studies in a large patient population. Patients and Methods: Data were obtained from 268 adult patients (163 males/105 females; median age, 54 years [range, 21 to 74 years]) with advanced solid tumors treated in phase I/II trials with cisplatin monotherapy or combination chemotherapy with etoposide, irinotecan, topotecan, or docetaxel. Cisplatin was administered either weekly (n = 93) or once every 3 weeks (n = 175) at dose levels of 50 to 100 mg/m2 (3-hour infusion). Analysis of 485 complete courses was based on measurement of total and non-protein-bound cisplatin in plasma by atomic absorption spectrometry. Results: No pharmacokinetic interaction was found between cisplatin and the anticancer drugs used in combination therapies. A linear correlation was observed between area under the curves of unbound and total cisplatin (r = 0.63). The mean plasma clearance of unbound cisplatin (CLfree) was 57.1 ± 14.7 L/h (range, 31.0 to 116 L/h), with an interpatient variability of 25.6%. BSA varied between 1.43 and 2.40 m2 (mean, 1.86 ± 0.19 m2), with an interpatient variability of 10.4%. When CLfree was corrected for BSA, interindividual variability remained in the same order (23.6 v 25.6%). Only a weak correlation was found between CLfree and BSA (r = 0.42). Intrapatient variability in CLfree, calculated from 90 patients was 12.1% ± 7.8% (range, 0.30% to 32.7%). Conclusion: In view of the high interpatient variability in CLfree relative to variation in observed BSA, no rationale for continuing BSA-based dosing was found. We recommend fixed-dosing regimens for cisplatin.
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Body-surface area-based dosing does not increase accuracy of predicting cisplatin exposure
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Autor/in / Beteiligte Person: | DE JONGH, Felix E ; VERWEIJ, Jaap ; LOOS, Walter J ; DE WIT, Ronald ; DE JONGE, Maja J. A ; PLANTING, André S. T ; NOOTER, Kees ; STOTER, Gerrit ; SPARREBOOM, Alex |
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Zeitschrift: | Journal of clinical oncology, Jg. 19 (2001), Heft 17, S. 3733-3739 |
Veröffentlichung: | Baltimore, MD: Lippincott Williams & Wilkins, 2001 |
Medientyp: | academicJournal |
Umfang: | print, 28 ref |
ISSN: | 0732-183X (print) |
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