Masson E, Zamboni W C
School of Pharmacy, Laval University, Montreal, Quebec, Canada.
Clin Pharmacokinet. 1997 Apr;32(4):324-43. doi: 10.2165/00003088-199732040-00005.
Cancer chemotherapy doses are empirical in that the majority are administered at a fixed dose (mg/m2 or mg/kg). One reason for this is the intrinsic sensitivity of the tumour or host cells to one particular chemotherapy agent is unknown. Therefore, the likelihood of response or toxicity is unpredictable a priori. This contrasts with antimicrobial chemotherapy where sensitivity (minimum inhibitory concentration) can be determined for a specific bacterium. The pharmacokinetics of cancer chemotherapy agents is also highly variable between patients. In addition, the small therapeutic index of these drugs, combined with the lack of good surrogate markers of toxicity or response, adds to the empiricism of the administration of cancer chemotherapy. In the past few years, numerous studies have established good relationships between systemic exposure to cancer chemotherapy and both response and toxicity. These relationships have been used to individualise chemotherapy dose administration a priori and a posteriori. Some examples of drugs which are individualised based on their pharmacokinetics are methotrexate, busulfan and carboplatin. Other examples of antineoplastic agents which may eventually be individualised based on their pharmacokinetics are mercaptopurine, fluorouracil, etoposide and teniposide, topotecan and suramin. New strategies are being investigated to improve the therapeutic index of cancer chemotherapy agents such as biomodulation, pharmacogenetics, circadian administration and the modification of drug scheduling. Pharmacokinetic studies have also played a major role in these areas. Thus, despite the empiricism associate with cancer chemotherapy administration, some progress has been made and shown to have an impact on outcome. However, more studies are needed to improve cancer chemotherapy administration.
癌症化疗剂量是经验性的，因为大多数剂量是以固定剂量（毫克/平方米或毫克/千克）给药的。这样做的一个原因是肿瘤或宿主细胞对一种特定化疗药物的内在敏感性是未知的。因此，反应或毒性的可能性在事先是不可预测的。这与抗微生物化疗形成对比，在抗微生物化疗中可以确定特定细菌的敏感性（最低抑菌浓度）。癌症化疗药物的药代动力学在患者之间也存在很大差异。此外，这些药物的治疗指数较小，再加上缺乏毒性或反应的良好替代标志物，增加了癌症化疗给药的经验性。在过去几年中，大量研究已经确立了全身暴露于癌症化疗与反应和毒性之间的良好关系。这些关系已被用于事先和事后个体化化疗剂量给药。基于其药代动力学进行个体化的药物示例包括甲氨蝶呤、白消安和卡铂。其他可能最终基于其药代动力学进行个体化的抗肿瘤药物示例包括巯嘌呤、氟尿嘧啶、依托泊苷和替尼泊苷、拓扑替康和苏拉明。正在研究新的策略来提高癌症化疗药物的治疗指数，如生物调节、药物遗传学、昼夜给药和药物给药方案的调整。药代动力学研究在这些领域也发挥了重要作用。因此，尽管癌症化疗给药存在经验性，但已经取得了一些进展并显示对结果有影响。然而，需要更多的研究来改进癌症化疗给药。
