Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose.
Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose.
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DOI：
10.1111/cas.12647
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发表时间：
2015-05
期刊：
影响因子：
5.7
通讯作者：
Tanigawara Y
中科院分区：
文献类型：
--
作者：
Kenmotsu H;Tanigawara Y
自1996年以来，多西他赛（Taxotere®）一直是癌症治疗中最重要的化疗药物之一。虽然在各种癌症领域进行了大量的临床研究，但日本和西方国家之间的标准剂量存在差异。本文综述了多西他赛的药代动力学、药效学和毒理学特征，解释了多西他赛剂量存在种族差异的原因，并进一步讨论了解决这一问题的方向。在美国和欧洲人群中，最初推荐剂量为100 mg/m2，每3周一次，而日本I期研究建议推荐剂量为60 mg/m2，每3周一次。在美国/欧洲和日本进行的多西他赛前瞻性群体药代动力学分析表明，药代动力学不存在种族差异。两项分析均表明多西他赛清除率与α1-酸性糖蛋白水平、肝功能、年龄和体表面积相关。在60 - 100 mg/m2剂量范围内，观察到多西他赛剂量增加与肿瘤缓解率增加之间的关系。多西他赛第1周期的血药浓度-时间曲线下面积（AUC）与至疾病进展时间显著相关。血液学毒性与多西他赛的AUC密切相关，与接受75-100 mg/m2剂量治疗的美国/欧洲患者相比，在接受60 mg/m2剂量治疗的日本患者中更常观察到重度血液学毒性。日本人群似乎对多西他赛的毒性更敏感。75 mg/m2的多西他赛剂量现在不仅在全球试验中，而且在最近的日本试验中也是标准剂量。虽然多西他赛的最佳剂量尚不清楚，但我们需要根据患者的状态和化疗的目标继续寻求多西他赛的适当剂量。
Docetaxel (Taxotere®) has been one of the most important chemotherapeutic drugs for cancer treatment since 1996. Although a large number of clinical studies have been conducted in various cancer fields, there is a discrepancy in the standard dose between Japan and Western countries. This article reviews the pharmacokinetic, pharmacodynamic and toxicological profiles of docetaxel, and explains why there exists an ethnic difference in dose, and further discusses which direction we should go forward to solve this problem. The original recommended dose was 100 mg/m2 every 3 weeks in US and European populations, while a Japanese phase I study suggested the recommended dose as 60 mg/m2 every 3 weeks. A prospective population pharmacokinetic analysis of docetaxel conducted in both the USA/Europe and Japan, indicated an absence of ethnic difference in the pharmacokinetics. Both analyses demonstrated that docetaxel clearance is related to α1-acid glycoprotein level, hepatic function, age and body surface area. The relationship was observed between increasing docetaxel dose and increased tumor response rates across the dose range of 60 to 100 mg/m2. The area under the serum concentration time curve (AUC) of docetaxel at the first cycle was significantly related to time to progression. Hematological toxicities were well correlated with the AUC of docetaxel, and severe hematological toxicities were more frequently observed in Japanese patients treated with 60 mg/m2, compared to the US/European patients treated with 75–100 mg/m2 dose. The Japanese population seems more susceptible to the toxicity of docetaxel. A docetaxel dose of 75 mg/m2 is now standard not only in global trials but also in recent Japanese trials. Although the optimal dose of docetaxel is still unclear, we need to continue to seek the appropriate dose of docetaxel depending on patient status and the goals of chemotherapy.
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影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1016/s1470-2045(10)70132-7
发表时间：
2010-07
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Herbst RS;Sun Y;Eberhardt WE;Germonpré P;Saijo N;Zhou C;Wang J;Li L;Kabbinavar F;Ichinose Y;Qin S;Zhang L;Biesma B;Heymach JV;Langmuir P;Kennedy SJ;Tada H;Johnson BE
通讯作者：
Johnson BE
影响因子：
45.3
作者：
Bruno, R;Hille, D;Sheiner, LB
通讯作者：
Sheiner, LB
影响因子：
6.7
作者：
Engels, FK;ten Tije, AJ;Sparreboom, A
通讯作者：
Sparreboom, A
影响因子：
6.7
作者：
Baker, S. D.;Verweij, J.;Sparreboom, A.
通讯作者：
Sparreboom, A.