Ryan Christopher W
Oregon Health and Science University Knight Cancer Institute, Portland, OR, USA.
J Oncol Pharm Pract. 2017 Jan;23(1):43-55. doi: 10.1177/1078155215618769. Epub 2016 Jul 9.
Within the past decade, treatment options for metastatic renal cell carcinoma have expanded dramatically. Currently, seven targeted agents are approved for use in metastatic renal cell carcinoma and have superseded the use of parenteral cytokine therapy with interleukin-2 or interferon, the former standards of care for metastatic renal cell carcinoma. Targeted agents include inhibitors of the vascular endothelial growth factor pathway (i.e. sorafenib, sunitinib, pazopanib, axitinib, and bevacizumab) and inhibitors of the mammalian target of rapamycin pathway (i.e. temsirolimus and everolimus). These newer therapies have been shown to improve progression-free survival compared with previous approaches. Because most of these targeted agents are taken orally, responsibility for dose administration has shifted to patients, which might result in variable adherence. Additionally, with new treatments for metastatic renal cell carcinoma comes the challenge of selecting dosing schemes that maximize therapeutic benefit and minimize adverse events. Much of the information related to the effectiveness of dose modifications for targeted therapies in metastatic renal cell carcinoma has been gathered from clinical studies that have strict inclusion and exclusion criteria, which might not translate directly to real-world patient populations. This review discusses the impact of dose adherence on the effectiveness of targeted agents to treat metastatic renal cell carcinoma, assesses the literature regarding the effectiveness of approved dosing strategies, and provides a summary of alternative dosing strategies.
在过去十年中，转移性肾细胞癌的治疗选择有了显著扩展。目前，有七种靶向药物被批准用于治疗转移性肾细胞癌，它们已取代了肠外细胞因子疗法（使用白细胞介素-2或干扰素），而后者曾是转移性肾细胞癌的标准治疗方法。靶向药物包括血管内皮生长因子途径抑制剂（即索拉非尼、舒尼替尼、帕唑帕尼、阿昔替尼和贝伐单抗）以及雷帕霉素靶蛋白途径抑制剂（即替西罗莫司和依维莫司）。与先前的治疗方法相比，这些新疗法已被证明可改善无进展生存期。由于这些靶向药物大多为口服给药，剂量管理的责任已转移至患者，这可能导致依从性参差不齐。此外，随着转移性肾细胞癌新治疗方法的出现，还面临着选择能使治疗效益最大化且不良事件最小化的给药方案的挑战。许多与转移性肾细胞癌靶向治疗剂量调整有效性相关的信息是从具有严格纳入和排除标准的临床研究中收集而来的，这些标准可能无法直接适用于真实世界的患者群体。本综述讨论了剂量依从性对靶向药物治疗转移性肾细胞癌有效性的影响，评估了有关已批准给药策略有效性的文献，并总结了替代给药策略。
