Body-surface area-based dosing does not increase accuracy of predicting cisplatin exposure
Body-surface area-based dosing does not increase accuracy of predicting cisplatin exposure
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DOI：
10.1200/jco.2001.19.17.3733
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发表时间：
2001-09-01
影响因子：
45.3
通讯作者：
Sparreboom, A
中科院分区：
文献类型：
--
作者：
de Jongh, FE;Verweij, J;Sparreboom, A
目的：大多数抗癌药物的剂量是基于体表面积（BSA），以减少药物效应的个体间差异。我们通过分析大量患者人群中前瞻性研究中获得的顺铂药代动力学，评估了这一概念与顺铂的相关性。（163名男性/105名女性;中位年龄，54岁[范围，21 - 74岁]），在1/11期试验中接受顺铂单药治疗或依托泊苷、伊立替康、拓扑替康或多西他赛联合化疗治疗的晚期实体瘤患者。顺铂每周一次（n = 93）或每3周一次（n = 175），剂量水平为50至100 mg/m2（3小时输注）。485个完整疗程的分析是基于测量总的和非蛋白结合的顺铂在血浆中通过原子吸收spectrometry.Results：没有发现顺铂和抗癌药物之间的药代动力学相互作用的组合疗法。未结合顺铂和总顺铂的曲线下面积之间观察到线性相关性（r = 0.63）。未结合顺铂（CL free）的平均血浆清除率为57.1 ± 14.7 L/h（范围：31.0 - 116 L/h），患者间变异性为25.6%。BSA在1.43和2.40 m（2）之间变化（平均值为1.86 +/- 0.19 m（2）），患者间变异性为10.4%。当CL空闲时。校正BSA后，个体间变异性保持相同顺序（23.6 v25.6%）。CL free与BSA之间仅存在弱相关性（r = 0.42）。根据90例患者计算的CL free患者内变异性为12.1% +/- 7.8%（范围：0.30%至32.7%）。相对于观察到的BSA的变化，没有发现继续以BSA为基础的给药的理由。我们推荐顺铂的固定剂量方案。(C)2001年，美国临床肿瘤学会。
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 1/11 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 (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 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. (C) 2001 by American Society of Clinical Oncology.