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英国新生儿和婴儿视网膜母细胞瘤患者使用卡铂治疗药物监测的效用。

Utility of carboplatin therapeutic drug monitoring for the treatment of neonate and infant retinoblastoma patients in the United Kingdom.

机构信息

Department of Paediatric Oncology, Birmingham Children's Hospital, Birmingham, UK.

Department of Paediatric Oncology, Great Ormond Street Hospital, London, UK.

出版信息

Br J Cancer. 2024 Aug;131(3):491-497. doi: 10.1038/s41416-024-02728-1. Epub 2024 Jun 13.

Abstract

BACKGROUND

Retinoblastoma is the most common intra-ocular malignancy in children and frequently presents in very young patients who commonly require intravenous carboplatin. Delivering this is challenging due to a lack of uniform dosing recommendations, rapid changes in physiological function and the risk of side-effects.

METHODS

We conducted a retrospective review of neonates and infants in the UK with retinoblastoma, who have undergone carboplatin therapeutic drug monitoring (TDM). We report on the pharmacokinetic, treatment efficacy and toxicity data.

RESULTS

In total, 29 patients (median age 5 weeks at treatment onset) underwent a total of 74 TDM guided cycles of chemotherapy, involving real time sampling and dose adjustment. An additional 13 patients underwent TDM sampling to modify doses between cycles. Without the adoption of TDM guided dosing, carboplatin exposures would have been ≥20% outside the target AUC in 38/78 (49%) of treatment cycles. Excellent responses and a reassuringly low incidence of toxicities were observed following dose adjustment, despite the young patient age and the implementation of dose increases in the majority of cases.

CONCLUSIONS

Real time TDM is safe, effective and deliverable for neonates and infants receiving carboplatin for retinoblastoma and should be considered standard of care up to the age of 6 months.

摘要

背景

视网膜母细胞瘤是儿童中最常见的眼内恶性肿瘤,常发生于非常年幼的患者,这些患者通常需要静脉注射卡铂。由于缺乏统一的剂量推荐、生理功能的快速变化以及副作用的风险,因此给这些患者用药具有挑战性。

方法

我们对在英国接受卡铂治疗药物监测(TDM)的患有视网膜母细胞瘤的新生儿和婴儿进行了回顾性研究。我们报告了药代动力学、治疗效果和毒性数据。

结果

共有 29 名患者(治疗开始时的中位年龄为 5 周)接受了总共 74 个 TDM 指导的化疗周期,包括实时采样和剂量调整。另有 13 名患者在治疗周期之间进行 TDM 采样以调整剂量。如果不采用 TDM 指导剂量,未经 TDM 指导剂量调整的情况下,在 78 个治疗周期中的 38 个(49%)中,卡铂暴露量将超过目标 AUC 的 20%。尽管患者年龄较小,且大多数情况下都增加了剂量,但在进行剂量调整后,观察到了极好的反应和令人放心的低毒性发生率。

结论

实时 TDM 对于接受卡铂治疗视网膜母细胞瘤的新生儿和婴儿是安全、有效和可行的,应在 6 个月大之前被视为标准护理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100f/11300439/a01993d25705/41416_2024_2728_Fig1_HTML.jpg

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