Barnett Shelby, Holden Victoria, Campbell-Hewson Quentin, Veal Gareth J
Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, United Kingdom.
Leeds General Infirmary, Leeds, United Kingdom.
Front Oncol. 2022 Jan 6;11:815040. doi: 10.3389/fonc.2021.815040. eCollection 2021.
The utility of Therapeutic Drug Monitoring (TDM) in the setting of childhood cancer is a largely underused tool, despite the common use of cytotoxic chemotherapeutics. While it is encouraging that modern advances in chemotherapy have transformed outcomes for children diagnosed with cancer, this has come at the cost of an elevated risk of life-changing long-term morbidity and late effects. This concern can limit the intensity at which these drugs are used. Widely used chemotherapeutics exhibit marked inter-patient variability in drug exposures following standard dosing, with fine margins between exposures resulting in toxicity and those resulting in potentially suboptimal efficacy, thereby fulfilling criteria widely accepted as fundamental for TDM approaches. Over the past decade in the UK, the paediatric oncology community has increasingly embraced the potential benefits of utilising TDM for particularly challenging patient groups, including infants, anephric patients and those receiving high dose chemotherapy. This has been driven by a desire from paediatric oncologists to have access to clinical pharmacology information to support dosing decisions being made. This provides the potential to modify doses between treatment cycles based on a comprehensive set of clinical information, with individual patient drug exposures being used alongside clinical response and tolerability data to inform dosing for subsequent cycles. The current article provides an overview of recent experiences of conducting TDM in a childhood cancer setting, from the perspectives of the clinicians, scientists and pharmacists implementing TDM-based dosing recommendations. The ongoing programme of work has facilitated investigations into the validity of current approaches to dosing for some of the most challenging childhood cancer patient groups, with TDM approaches now being expanded from well-established cytotoxic drugs through to newer targeted treatments.
尽管细胞毒性化疗药物在儿童癌症治疗中普遍使用，但治疗药物监测（TDM）在儿童癌症治疗中的作用在很大程度上未得到充分利用。令人鼓舞的是，化疗的现代进展改变了被诊断患有癌症儿童的治疗结果，但这是以长期发生改变生活的发病率和晚期效应的风险升高为代价的。这种担忧可能会限制这些药物的使用强度。广泛使用的化疗药物在标准给药后，患者之间的药物暴露存在显著差异，暴露量导致毒性和导致潜在次优疗效之间的界限很细微，从而满足了被广泛接受为TDM方法基础的标准。在过去十年中，在英国，儿科肿瘤学界越来越多地接受了将TDM用于特别具有挑战性的患者群体的潜在益处，包括婴儿、无肾患者和接受高剂量化疗的患者。这是由儿科肿瘤学家希望获得临床药理学信息以支持给药决策的愿望所驱动的。这提供了根据一套全面的临床信息在治疗周期之间调整剂量的可能性，将个体患者的药物暴露与临床反应和耐受性数据一起用于为后续周期确定给药剂量。本文从实施基于TDM的给药建议的临床医生、科学家和药剂师的角度，概述了在儿童癌症环境中进行TDM的近期经验。正在进行的工作项目促进了对一些最具挑战性的儿童癌症患者群体当前给药方法有效性的研究，TDM方法现在正从成熟的细胞毒性药物扩展到更新的靶向治疗。
