Children's Cancer Centre, Royal Children's Hospital, Parkville, Victoria, Australia.
Neurodisability and Rehabilitation - Clinical Sciences, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Cancer Rep (Hoboken). 2021 Dec;4(6):e1404. doi: 10.1002/cnr2.1404. Epub 2021 May 3.
Significant challenges persist in treating children with rare, relapsed, or refractory malignancies. Novel molecularly targeted drugs promise improved outcomes for these children with reduced toxicity. However, there is often limited evidence to substantiate their clinical efficacy and guide their use. This raises issues for clinical decision-making, ethical concerns surrounding equity of access to these often-expensive agents, and the management of families' expectations for cure. This audit evaluated the off-label use of novel drugs and associated clinical outcomes in order to guide the development of future clinical and ethical guidelines.
To evaluate the patterns in the off-label use of novel drugs for treating childhood cancer and the associated clinical outcomes to guide prospective studies and inform ethical and clinical governance protocols for the use of these agents.
A retrospective audit was performed for all patients who received novel drugs off-label as treatment for their malignancy at an Australian pediatric oncology center between 2010 and 2019.
One hundred patients with 32 unique diagnoses received 133 novel drugs across 124 regimens. Eighty-four patients received these drugs at the second line of treatment or greater. Novel drug median cost was $15 521 AUD (Range: $6.53 AUD to $258 339 AUD) and was primarily funded by the hospital (N = 60/133, 45.1%) or compassionate access from pharmaceutical companies (N = 52/133, 39.1%). Decision-making related to novel drugs was inconsistently documented. Ninety-one of 124 treatment regimens commenced between 2010 and 2019 resulted in objective responses (73.4%), but only 35 were still ongoing upon review in June 2020 (38.5%). Median response duration was 12.6 months (Range: 0-93.2 months).
While novel drugs were largely unable to definitively cure patients, most achieved objective responses. Prospective trials and more rigorous documentation are needed to fully inform the future use of these agents given the heterogeneity of their applications.
在治疗儿童罕见、复发或难治性恶性肿瘤方面仍然存在重大挑战。新型分子靶向药物有望为这些儿童带来更好的结果，同时降低毒性。然而，这些药物的临床疗效往往缺乏充分证据支持，其使用也存在争议。这给临床决策带来了问题，也引发了有关公平获得这些昂贵药物的伦理问题，以及对家庭治愈期望的管理问题。本审计评估了新型药物的标签外使用及其相关临床结果，以指导未来的临床和伦理指南的制定。
评估新型药物治疗儿童癌症的标签外使用模式及其相关临床结果，以指导前瞻性研究，并为这些药物的使用提供伦理和临床治理协议。
对 2010 年至 2019 年期间在澳大利亚儿科肿瘤中心接受新型药物标签外治疗恶性肿瘤的所有患者进行了回顾性审计。
100 名患者有 32 种独特的诊断，共接受了 133 种新型药物，共 124 种方案。84 名患者在二线或更高线治疗中接受了这些药物。新型药物的中位费用为 15521 澳元（范围：6.53 澳元至 258339 澳元），主要由医院（N=60/133，45.1%）或制药公司的慈善准入（N=52/133，39.1%）资助。与新型药物相关的决策记录不一致。2010 年至 2019 年期间开始的 124 种治疗方案中有 91 种（73.4%）产生了客观反应，但在 2020 年 6 月审查时仍在进行的只有 35 种（38.5%）。中位反应持续时间为 12.6 个月（范围：0-93.2 个月）。
虽然新型药物在很大程度上无法明确治愈患者，但大多数患者都有客观反应。鉴于这些药物的应用具有异质性，需要进行前瞻性试验和更严格的记录，以充分了解这些药物的未来应用。
