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

Purpose: Most anticancer drugs are dosed based on body-surface area (BSA) t o reduce interindividual variability of drug effects. We evaluated the rele vance 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 s olid tumors treated in phase 1/11 trials with cisplatin monotherapy or comb ination chemotherapy with etoposide, irinotecan, topotecan, or docetaxel. C isplatin 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 48 5 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 o bserved 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 m(2) (mean, 1.86 +/- 0.19 m(2)), with a n interpatient variability of 10.4%. When CLfree. Was corrected for BSA, in terindividual 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% (ran ge, 0.30% to 32.7%). Conclusion: In view of the high interpatient variability in CLfree. relativ e to variation in observed BSA, no rationale for continuing BSA-based dosin g was found. We recommend fixed-dosing regimens for cisplatin. (C) 2001 by American Society of Clinical Oncology.