Retinoids are vitamin A derivatives and include trans-retinoic acid, isotretinoin, tamibarotene, and bexarotene, all of which are currently available for clinical use. The clinical development of retinoid therapy for neuroblastoma has a history spanning more than four decades. The most promising agent is isotretinoin, which can contribute to improving event-free survival in patients with high-risk neuroblastoma by approximately 10% when administered over six months as maintenance therapy. Although isotretinoin is regarded as an essential component in the standard clinical management of high-risk neuroblastoma, its use for this purpose in the US and EU is off-label. To promote isotretinoin use in Japan as a treatment for neuroblastoma, our clinical research team is planning to launch an investigator-initiated, registration-directed clinical trial. The present review article discusses the basic science behind retinoid therapy, pre-clinical/clinical evidence on neuroblastoma, the concept of the proposed clinical trial, and prospects for this therapy.
维甲酸类药物是维生素A衍生物，包括全反式维甲酸、异维甲酸、他米巴罗汀和贝沙罗汀，目前均已投入临床应用。维甲酸疗法治疗神经母细胞瘤的临床发展历程已跨越四十余年。其中最具前景的药物是异维甲酸，该药物作为维持治疗持续给药六个月时，可使高危神经母细胞瘤患者的无事件生存率提升约10%。尽管异维甲酸被视为高危神经母细胞瘤标准临床治疗的重要组成，但其在美国和欧盟用于此适应症仍属超说明书用药。为推进异维甲酸在日本作为神经母细胞瘤治疗药物的应用，我们的临床研究团队正计划启动一项研究者发起、以注册为导向的临床试验。本综述将系统阐述维甲酸疗法的科学基础、针对神经母细胞瘤的临床前/临床证据、拟议临床试验的设计理念以及该疗法的应用前景。
Retinoid Therapy for Neuroblastoma: Historical Overview, Regulatory Challenges, and Prospects
肿瘤(癌症)患者之家