Tissue engineering's green shoots of disruptive innovation.
Tissue engineering's green shoots of disruptive innovation.
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组织工程颠覆性创新的萌芽。
DOI：
10.1016/s0140-6736(14)60533-x
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Birchall MA
中科院分区：
文献类型：
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作者：
Birchall MA
报告的不良事件与索拉非尼已知的安全性数据相似。不良事件导致 64% 的患者减少剂量，19% 的患者退出研究。尽管Brose及其同事没有报告罕见的严重不良事件（<2%）或发生频率低于10%的所有级别不良事件，但临床医生应该意识到血管内皮生长因子受体靶向多激酶抑制剂（包括索拉非尼）的类别效应，这些效应会导致罕见的严重毒性，例如出血、血栓栓塞、肠穿孔和左心室功能障碍。因此，当患者接受索拉非尼治疗时，密切监测、早期识别和管理不良事件至关重要。对于本试验中 61% 患者的肿瘤基因型数据，甲状腺乳头状癌中 BRAF 突变频率 (46%) 较低，RAS 突变频率 (18%) 高于已报道的索拉非尼 2 期试验。 BRAF 和 RAS 突变均不能预测对索拉非尼的反应。尽管对参加我们 2 期试验的患者进行的一系列新颖影像学和肿瘤活检相关研究表明，索拉非尼抑制了甲状腺肿瘤中的 BRAF 和血管内皮生长因子通路，但 8 哪种通路对索拉非尼的疗效更重要仍不清楚。Brose 及其同事的试验结果 1 为进行性放射性碘难治性分化型甲状腺癌建立了新的护理标准，这是开发有效疗法的一项非凡成就。为了持续取得进展，我们需要发现更有效、更低毒性的治疗方法。未来的研究工作需要回答几个关键问题——治疗开始的时机、最佳剂量和时间表、一种多激酶抑制剂相对于另一种多激酶抑制剂或BRAF抑制剂相对于血管内皮生长因子受体抑制剂的优越性、作用机制、
The reported adverse events are similar to known safety data for sorafenib. Adverse events led to dose reductions in 64% and withdrawal from the study in 19% of patients. Although Brose and colleagues did not report rare serious adverse events (< 2%) or all-grade adverse events occurring at a frequency below 10%, clinicians should be aware of the class effects of vascular endothelial growth factor receptor-targeted multikinase inhibitors, including sorafenib, that result in rare serious toxicities such as bleeding, thromboembolism, bowel perforation, and left ventricle dysfunction. Close monitoring, early recognition, and management of adverse events are therefore essential when patients are being treated with sorafenib. For the tumour genotype data that were available in 61% of patients in this trial, the frequency of BRAF mutation (46%) was lower and that of RAS mutation (18%) higher in papillary thyroid carcinoma than in reported phase 2 trials of sorafenib. Neither BRAF nor RAS mutations predicted a response to sorafenib. Although serial novel imaging and tumour biopsy correlative studies done in patients enrolled in our phase 2 trial showed that sorafenib inhibited BRAF and vascular endothelial growth factor pathways in thyroid tumours, 8 which pathway is more important for the efficacy of sorafenib remains unclear.The results of Brose and colleagues’ trial1 establish a new standard of care for progressive radioactive iodine-refractory differentiated thyroid cancer, which is an extraordinary achievement in the development of effective therapies. To make continued progress, we need to discover treatments with better effectiveness and lower toxicity. Future research efforts need to answer several key questions—timing of treatment initiation, optimum dose and schedule, superiority of one multikinase inhibitor over another or BRAF inhibitors over vascular endothelial growth factor receptor inhibitors, mechanisms of action,