Division of Hematology-Oncology, Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-8852, USA.
J Clin Oncol. 2013 Mar 10;31(8):1009-20. doi: 10.1200/JCO.2012.43.7459. Epub 2013 Feb 11.
Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non-small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non-cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting.
尽管维持治疗在治疗某些血液恶性肿瘤方面已经得到了很好的应用，但它最近才成为治疗晚期非小细胞肺癌的一种治疗模式。维持治疗旨在延长完成规定数量诱导化疗周期后的临床有利状态，它有两种主要模式。持续维持治疗需要持续使用初始化疗方案的一部分，通常是非铂类细胞毒性药物或分子靶向药物。而切换维持（也称为序贯治疗）则是在一线化疗完成后立即引入新的、可能具有非交叉耐药性的药物。维持治疗的潜在理由包括增加有效治疗的暴露、降低化疗耐药性、优化化疗药物的疗效、抗血管生成作用和改变抗肿瘤免疫。迄今为止，培美曲塞和厄洛替尼的切换维持治疗策略已显示出总生存期的改善，这导致了美国食品和药物管理局对此适应证的批准。最近，培美曲塞的持续维持治疗也被发现可以延长总生存期。预测维持化疗获益的因素包括对一线治疗的反应程度、体能状态、进展时进一步接受治疗的可能性、肿瘤组织学和分子特征。维持治疗的几个方面在胸肿瘤学领域引起了相当大的争议，包括临床试验终点、二线化疗的应用率、无治疗间隔的作用、生活质量、经济考虑以及无进展生存期是否是这种疾病治疗的一个有价值的目标。
