Bordeaux University Victor Se´galen, Bordeaux University Hospital, Hôpital Saint André, Bordeaux, France
Oncologist. 2011;16 Suppl 2(Suppl 2):32-44. doi: 10.1634/theoncologist.2011-S2-32.
Targeted therapy for advanced renal cell carcinoma (RCC) has recently expanded the available treatment options for patients with these malignancies. The rapid introduction of novel treatment options into clinical practice within a relatively short time frame has created some new challenges pertaining to adverse event (AE) management in patients with advanced RCC. Accumulating safety data from the pivotal phase III clinical trials of the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab plus interferon, VEGF receptor tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), and mammalian target of rapamycin inhibitors (temsirolimus and everolimus) have served to characterize the toxicity profiles of these novel agents. Overall, it is evident that RCC-directed targeted therapy differs from immunotherapy and cytotoxic chemotherapy in terms of a number of unique nonhematologic AEs (some of which have not been traditionally encountered in oncology practice) and that there are distinctions within and across the various classes of agents with respect to the most prominent AEs and the risk for less common but serious complications. Although treatment-associated AEs are common, the majority of AEs reported during clinical trial experiences were grade 1 or 2 in severity and manageable with intervention in the form of supportive measures and/or dosage modification. Therefore, despite the relatively complex AE profiles of RCC-directed targeted therapy, patient education, consistent monitoring with a focus on early detection by health care providers (oncologists, general physicians, nurses), and the application of emerging AE management strategies may allow for prolonged treatment in most patients with advanced RCC.
晚期肾细胞癌(RCC)的靶向治疗最近扩大了这些恶性肿瘤患者的可用治疗选择。新型治疗选择在相对较短的时间内迅速引入临床实践,给晚期 RCC 患者的不良事件(AE)管理带来了一些新的挑战。来自抗血管内皮生长因子(VEGF)抗体贝伐珠单抗联合干扰素、VEGF 受体酪氨酸激酶抑制剂(舒尼替尼、索拉非尼和帕唑帕尼)和哺乳动物雷帕霉素靶蛋白抑制剂(替西罗莫司和依维莫司)的关键 III 期临床试验的累积安全性数据有助于确定这些新型药物的毒性特征。总的来说,很明显,RCC 靶向的靶向治疗在许多独特的非血液学 AE 方面与免疫治疗和细胞毒性化疗不同(其中一些在肿瘤学实践中尚未遇到),并且在各种药物类别中,在最突出的 AE 和不太常见但严重的并发症的风险方面存在差异。尽管治疗相关的 AE 很常见,但临床试验经验中报告的大多数 AE 严重程度为 1 级或 2 级,可通过支持性措施和/或剂量调整进行干预来管理。因此,尽管 RCC 靶向的靶向治疗的 AE 谱相对复杂,但对患者进行教育、持续监测(重点是医疗保健提供者(肿瘤学家、普通医师、护士)早期发现),并应用新兴的 AE 管理策略,可能允许大多数晚期 RCC 患者延长治疗时间。