Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Curr Oncol Rep. 2013 Apr;15(2):91-7. doi: 10.1007/s11912-013-0292-x.
The introduction of targeted therapies, specifically those that target the VEGF receptor (VEGFR), PDGF receptor (PDGFR) and the mTOR pathways, has significantly changed the approach to patients with unresectable renal cell cancer (RCC). However, drug resistance develops through bypassing of targeted pathways. Regorafenib (BAY 73-4506) is a novel bi-aryl urea compound that has potential anti-tumour activity in RCC, as along with targeting VEGF and PDGF receptors, it targets additional kinases associated with alternative pathways of angiogenesis and resistance to VEGF-targeted drugs. Based on a phase II clinical trial, the efficacy outcome of regorafenib in the first-line setting of unresectable RCC appears comparable that of other targeted first-line drugs. However, testing regorafenib in standard phase III trials seems inappropriate in view of its toxic effects. Further assessment of regorafenib should exploit the drug's ability to inhibit mechanisms of escape from anti-angiogenic treatment through biomarker-driven clinical trials.
靶向治疗的引入，特别是针对血管内皮生长因子受体（VEGFR）、血小板衍生生长因子受体（PDGFR）和 mTOR 通路的靶向治疗，已经显著改变了不可切除肾细胞癌（RCC）患者的治疗方法。然而，药物耐药性通过靶向途径的旁路而产生。regorafenib（BAY 73-4506）是一种新型双芳基脲化合物，在 RCC 中具有潜在的抗肿瘤活性，因为它不仅靶向 VEGF 和 PDGF 受体，还靶向与血管生成和对 VEGF 靶向药物耐药性的替代途径相关的其他激酶。基于一项 II 期临床试验，regorafenib 在不可切除 RCC 的一线治疗中的疗效结果似乎与其他靶向一线药物相当。然而，鉴于其毒性作用，在标准 III 期试验中测试 regorafenib 似乎并不合适。进一步评估 regorafenib 应该利用该药抑制抗血管生成治疗逃逸机制的能力，通过生物标志物驱动的临床试验进行。
