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舒尼替尼持续每日给药治疗胰腺神经内分泌肿瘤患者的学习经验。

Learning experiences with sunitinib continuous daily dosing in patients with pancreatic neuroendocrine tumours.

作者信息

Raymond E, Faivre S

机构信息

Medical Oncology, Beaujon University Hospital, Clichy, France.

出版信息

Curr Oncol. 2014 Dec;21(6):309-17. doi: 10.3747/co.21.1647.

Abstract

Molecular strategies to improve outcomes for patients with pancreatic neuroendocrine tumours (nets) have focused on targeting vascular endothelial growth factor, platelet-derived growth factor, and mtor (the mammalian target of rapamycin). This approach has led to the regulatory approval of two molecularly targeted agents for advanced pancreatic nets: sunitinib, a multi-targeted tyrosine kinase inhibitor, and everolimus, an mtor inhibitor. Initial experience with sunitinib in advanced pancreatic net was gained from the phase iii registration trial, which used a continuous daily dosing (cdd) schedule instead of daily drug administration for 4 consecutive weeks every 6 weeks (schedule 4/2), the approved schedule for advanced renal cell carcinoma (rcc) and gastrointestinal stromal tumour (gist). Clinical experience gained with schedule 4/2 in rcc and gist shows that, using a therapy management approach, patients can start and be maintained on the recommended dose and schedule, thus optimizing treatment outcomes. Here, we discuss challenges that can potentially be faced by physicians who use sunitinib on the cdd schedule, and we use clinical data and real-life clinical experience to present therapy management approaches that support cdd in advanced pancreatic net.

摘要

改善胰腺神经内分泌肿瘤(NETs)患者预后的分子策略主要集中在靶向血管内皮生长因子、血小板衍生生长因子和mTOR(雷帕霉素的哺乳动物靶点)。这种方法已使两种分子靶向药物获批用于晚期胰腺NETs:舒尼替尼,一种多靶点酪氨酸激酶抑制剂;依维莫司,一种mTOR抑制剂。舒尼替尼用于晚期胰腺NET的初始经验来自III期注册试验,该试验采用每日持续给药(CDD)方案,而非晚期肾细胞癌(RCC)和胃肠道间质瘤(GIST)获批的方案,即每6周连续4周每日给药(4/2方案)。RCC和GIST采用4/2方案的临床经验表明,通过治疗管理方法,患者可以开始并维持在推荐剂量和方案上,从而优化治疗效果。在此,我们讨论使用舒尼替尼CDD方案的医生可能面临的挑战,并利用临床数据和实际临床经验介绍支持晚期胰腺NETs采用CDD方案的治疗管理方法。

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