Body-surface area-based dosing does not increase accuracy of predicting cisplatin exposure.

Abstract

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/m(2) (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 (CL(free)) 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 m(2) (mean, 1.86 +/- 0.19 m(2)), with an interpatient variability of 10.4%. When CL(free) was corrected for BSA, interindividual variability remained in the same order (23.6 v 25.6%). Only a weak correlation was found between CL(free) and BSA (r = 0.42). Intrapatient variability in CL(free), calculated from 90 patients was 12.1% +/- 7.8% (range, 0.30% to 32.7%).

CONCLUSION:

In view of the high interpatient variability in CL(free) relative to variation in observed BSA, no rationale for continuing BSA-based dosing was found. We recommend fixed-dosing regimens for cisplatin.

• Authors: F E de Jongh, J Verweij, W J Loos, R de Wit, M J de Jonge, A S Planting, K Nooter, G Stoter, A Sparreboom
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 17 Pg. 3733-9 (Sep 01 2001) ISSN: 0732-183X [Print] United States
• PMID: 11533095 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Cisplatin

Topics

• Adult
• Aged
• Analysis of Variance
• Antineoplastic Agents (administration & dosage, pharmacokinetics)
• Body Surface Area
• Cisplatin (administration & dosage, pharmacokinetics)
• Dose-Response Relationship, Drug
• Female
• Humans
• Linear Models
• Male
• Metabolic Clearance Rate
• Middle Aged
• Prospective Studies
• Sex Factors
• Statistics, Nonparametric