Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK.
Division of Cancer Sciences, University of Manchester, Manchester, UK.
Br J Clin Pharmacol. 2021 Feb;87(2):256-262. doi: 10.1111/bcp.14419. Epub 2020 Jun 24.
The widely used platinum agent carboplatin represents a good example of an anticancer drug where clear relationships between pharmacological exposure and clinical response and toxicity have previously been shown. Within the setting of childhood cancer, there are defined groups of patients who present a particular challenge when dosing with carboplatin, including neonates and infants, those who are anephric, and poor prognosis patients receiving high-dose chemotherapy. For these groups, nonstandard chemotherapy dosing regimens are currently utilised, often with different approaches between clinical study protocols and between treatment centres. For the treatment of these patient populations in the UK, there is now significant experience in carrying out therapeutic drug monitoring, aiming to consistently achieve target drug exposures, maximise drug efficacy and minimise treatment-related side effects. An ongoing clinical trial is currently providing information on drug exposure for a wide range of anticancer agents in these hard to treat patient populations. In addition to supporting dosing decisions for individual patients, the collection and analysis of these data may allow the development of future dosing regimens. For example, current reduced dosing approaches for neonates and infants based on age or body weight, may well be better replaced by regimens based on a sound pharmacological rationale. The successful use of adaptive carboplatin dosing in childhood cancer should encourage the development of therapeutic drug monitoring approaches more widely in an oncology setting.
广泛使用的铂类药物卡铂就是一个很好的例子,它的药理作用与临床反应和毒性之间存在明确的关系。在儿童癌症中,有一些特定的患者群体在使用卡铂进行治疗时存在特殊的挑战,包括新生儿和婴儿、无肾功能的患者以及接受高剂量化疗的预后不良的患者。对于这些群体,目前正在使用非标准的化疗剂量方案,这些方案在临床研究方案和治疗中心之间往往存在不同的方法。在英国,目前在为这些患者群体进行治疗时,已经有了进行治疗药物监测的丰富经验,旨在持续实现目标药物暴露,最大程度提高药物疗效并最小化治疗相关的副作用。目前正在进行一项临床试验,为这些难以治疗的患者群体中的广泛抗癌药物提供药物暴露信息。除了为个别患者的剂量决策提供支持外,这些数据的收集和分析还可能为未来的剂量方案制定提供依据。例如,目前基于年龄或体重的新生儿和婴儿的降低剂量方法,很可能会被基于合理药理学原理的方案所取代。在儿童癌症中成功使用适应性卡铂剂量应鼓励在肿瘤学领域更广泛地发展治疗药物监测方法。