Fiore Michele, D Apos Angelillo Rolando Maria, Greco Carlo, Fioroni Iacopo, Ippolito Edy, Santini Daniele, Ramella Sara
Radiation Oncology, Campus Bio-Medico University, Rome, Italy.
Medical Oncology Unit, Campus Bio-Medico University, Rome, Italy.
Chemotherapy. 2018 Mar 19;63(2):83-89. doi: 10.1159/000488252.
Treatment of metastatic renal cell carcinoma (mRCC) has seen substantial progress over the last decade. A number of targeted therapies have been shown to improve clinical outcome. Vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKIs) are an effective option in treating mRCC. RCC is traditionally perceived to be a radioresistant malignancy with a limited role of radiotherapy (RT) in the management of localized disease. While RCC appears to be radioresistant using conventionally fractionated RT, preclinical data suggest increased radiosensitivity when an ablative, hypofractionated schedule is used. RT is a common treatment for metastases; therefore, it is important to understand how best to use the combination of RT with targeted therapies. Preclinical studies have suggested that the combination of anti-angiogenic drugs with RT enhances the therapeutic effect compared with ionizing radiation alone. However, clinical data gave rise to warnings due to an increased incidence of severe gastrointestinal side effects. This article reviews the literature behind the preclinical and clinical data of the combination of RT with VEGFR-TKIs currently approved for RCC (sunitinib, sorafenib, pazopanib, and axitinib), with a focus on dose schedules as well as efficacy and toxicity.
在过去十年中，转移性肾细胞癌（mRCC）的治疗取得了重大进展。多种靶向治疗已被证明可改善临床结局。血管内皮生长因子受体（VEGFR）-酪氨酸激酶抑制剂（TKIs）是治疗mRCC的有效选择。传统上，肾细胞癌被认为是一种对放疗耐药的恶性肿瘤，放疗（RT）在局限性疾病管理中的作用有限。虽然使用传统分割放疗时肾细胞癌似乎对放疗耐药，但临床前数据表明，采用消融性大分割放疗方案时，放射敏感性会增加。放疗是转移灶的常见治疗方法；因此，了解如何最佳地将放疗与靶向治疗联合使用很重要。临床前研究表明，与单独使用电离辐射相比，抗血管生成药物与放疗联合使用可增强治疗效果。然而，临床数据因严重胃肠道副作用的发生率增加而发出警告。本文回顾了目前已获批用于肾细胞癌的VEGFR-TKIs（舒尼替尼、索拉非尼、帕唑帕尼和阿昔替尼）与放疗联合使用的临床前和临床数据背后的文献，重点关注剂量方案以及疗效和毒性。
