Pal Sumanta Kumar, Vogelzang Nicholas J
Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
Clin Adv Hematol Oncol. 2013 Mar;11(3):146-55.
Molecularly-targeted therapies have revolutionized the treatment of metastatic renal cell carcinoma (mRCC), but unmet needs remain. Efficacy of targeted agents is transient, and questions regarding optimal sequencing of therapies and benefits versus risks of combination therapy remain largely unanswered. In this article, an overview of ongoing/recently completed clinical trials evaluating sequential treatment strategies and combination therapy regimens is presented, along with a brief discussion of predictive biomarkers and prognostic factors. Several ongoing/recently completed clinical studies have been designed to help address 2 major questions currently facing physicians treating patients with mRCC: 1) What is the optimal sequence of targeted agents? and 2) Does combination therapy with targeted agents benefit patients with mRCC? Results of these trials may help establish the degree to which cross-resistance between agents occurs and which agents, when used consecutively, are associated with the most favorable outcomes. Clinical trial data maturing in the next 1-2 years should provide insight into the most effective treatment sequences and the benefits versus risks of combination therapies. Whether results of these studies will lead to a paradigm shift in treatment recommendations for patients with mRCC remains to be determined.
分子靶向治疗彻底改变了转移性肾细胞癌（mRCC）的治疗方式，但仍存在未满足的需求。靶向药物的疗效是短暂的，关于治疗的最佳顺序以及联合治疗的获益与风险等问题在很大程度上仍未得到解答。本文概述了正在进行/最近完成的评估序贯治疗策略和联合治疗方案的临床试验，并简要讨论了预测性生物标志物和预后因素。几项正在进行/最近完成的临床研究旨在帮助解决目前治疗mRCC患者的医生面临的两个主要问题：1）靶向药物的最佳顺序是什么？2）靶向药物联合治疗对mRCC患者有益吗？这些试验的结果可能有助于确定药物之间交叉耐药的程度，以及哪些药物连续使用时与最有利的结果相关。未来1 - 2年内成熟的临床试验数据应能深入了解最有效的治疗顺序以及联合治疗的获益与风险。这些研究的结果是否会导致mRCC患者治疗推荐的范式转变仍有待确定。
