非小细胞肺癌一线化疗结束后维持治疗的现状与争论(2)
分子医学的启动，使我们的治疗方法更有效。尽管如此，由于生物制剂和细胞毒药物都非常昂贵，需要继续研究这些以找到更敏感更有效的维持治疗方法。决定立即维持治疗还是等待二线治疗对每个病人和临床肿瘤学家来说仍然需要漫长的讨论和研究。
Ⅲ.小结
在过去的两年中，我们已经看到了治疗NSCLC取得的一些进步且现在有几个因素在治疗决策中发挥着重要作用，维持治疗已经加入NSCLC的治疗。更多的研究工作需要进行，以确定哪些患者真正适合维持治疗，因此，预测和预后生物标记物的发展对NSCLC患者是至关重要的，我们可以挑选出哪些患者适合治疗，以避免为每个人进行无差别治疗。然而，基于我们发现的这些机制，数据显示对于那些获得SD或对肺癌初始治疗有疗效的患者可以进行维持治疗。
Ⅳ.问题与展望
目前，NSCLC一线治疗结束后维持治疗在临床试验研究中仍然存在许多问题：(1)维持治疗的标准尚待统一：维持治疗主要针对NSCLC有效控制者；(2)维持治疗持续时间待统一：原则上维持治疗是持续到疾病进展或出现不能耐受毒副反应为止，但维持化疗的毒性反应可在体内蓄积，可能导致过度治疗；(3)晚期NSCLC患者接受维持治疗的疗效是否优于疾病进展后二线治疗的疗效有待于进一步临床试验研究，这一问题包括在本文中提到的立即还是延迟维持治疗孰优孰劣的问题，不同的化疗药物有不同的作用，哪些患者适合哪些化疗药物，以及在维持治疗中，这些问题都需要进一步进行大量实验研究才能证实。
, http://www.100md.com
参考文献：
[1] Socinski MA, Schell MJ, Peterman A et al. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small cell lung cancer. J. Clin. Oncol. 20(5), 1335–1343 (2002).
[2] Ciuleanu T, Brodowicz T, Zielinski et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non small cell lung cancer: a randomized, double blind, Phase 3 study. Lancet 374, 1432–1440 (2009).
, 百拇医药
[3] Cappuzzo F, Coudert BP, Wierzbicki R et al. Efficacy and safety of erlotinib as first-line maintenance in NSCLC following non-progression with chemotherapy: results from the Phase III SATURN study. Presented at: 13th World Lung Cancer Conference. San Francisco, CA, USA, 31 July–4 August 2009.
[4] Fidias PM, Dakhil SR, Lyss AP et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J. Clin. Oncol. 27, 591–598 (2009).
, http://www.100md.com
[5] Abali H, Disel U, Köse F et al. Immediate or delayed docetaxel: does progression-free survival really reflect two strategies? J. Clin. Oncol. 27(17), 2889 (2009).
[6] Ciuleanu T, Brodowicz T, Zielinski et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non small cell lung cancer: a randomized, double blind, Phase 3 study. Lancet 374, 1432–1440 (2009).
[7] Peterson P, Park K, Fossella F et al. Is pemetrexed more effective in adenocarcinoma and large cell lung cancer than in squamous cell carcinoma? A retrospective analysis of a Phase III trial of pemetrexed vs docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC): P2-328. J. Thorac. Oncol. 2(Suppl. 4), s851 (2007).
, 百拇医药
[8] Scagliotti GV, Parikh P, von Pawel J et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy naive patients with advanced stage non-small-cell lung cancer. J. Clin. Oncol. 26, 3543–3551 (2008).
[9] Brugger W, Kim J-H, Hansen O et al. Biomarker analyses from SATURN a Phase III placebo controlled study of erlotinib as first line maintenance therapy for advanced NSCLC. Eur. J. Cancer 7(2 Suppl.), 559, (2009) (Abstract 9176).
, http://www.100md.com
[10]Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 361(10), 947–957 (2009).
[11]Pirker R, Pereira JR, Szczesna A et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised Phase III trial. Lancet 373(9674), 1525–1531 (2009)., http://www.100md.com(张春玲 刘凤娟)
Ⅲ.小结
在过去的两年中，我们已经看到了治疗NSCLC取得的一些进步且现在有几个因素在治疗决策中发挥着重要作用，维持治疗已经加入NSCLC的治疗。更多的研究工作需要进行，以确定哪些患者真正适合维持治疗，因此，预测和预后生物标记物的发展对NSCLC患者是至关重要的，我们可以挑选出哪些患者适合治疗，以避免为每个人进行无差别治疗。然而，基于我们发现的这些机制，数据显示对于那些获得SD或对肺癌初始治疗有疗效的患者可以进行维持治疗。
Ⅳ.问题与展望
目前，NSCLC一线治疗结束后维持治疗在临床试验研究中仍然存在许多问题：(1)维持治疗的标准尚待统一：维持治疗主要针对NSCLC有效控制者；(2)维持治疗持续时间待统一：原则上维持治疗是持续到疾病进展或出现不能耐受毒副反应为止，但维持化疗的毒性反应可在体内蓄积，可能导致过度治疗；(3)晚期NSCLC患者接受维持治疗的疗效是否优于疾病进展后二线治疗的疗效有待于进一步临床试验研究，这一问题包括在本文中提到的立即还是延迟维持治疗孰优孰劣的问题，不同的化疗药物有不同的作用，哪些患者适合哪些化疗药物，以及在维持治疗中，这些问题都需要进一步进行大量实验研究才能证实。
, http://www.100md.com
参考文献：
[1] Socinski MA, Schell MJ, Peterman A et al. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small cell lung cancer. J. Clin. Oncol. 20(5), 1335–1343 (2002).
[2] Ciuleanu T, Brodowicz T, Zielinski et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non small cell lung cancer: a randomized, double blind, Phase 3 study. Lancet 374, 1432–1440 (2009).
, 百拇医药
[3] Cappuzzo F, Coudert BP, Wierzbicki R et al. Efficacy and safety of erlotinib as first-line maintenance in NSCLC following non-progression with chemotherapy: results from the Phase III SATURN study. Presented at: 13th World Lung Cancer Conference. San Francisco, CA, USA, 31 July–4 August 2009.
[4] Fidias PM, Dakhil SR, Lyss AP et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J. Clin. Oncol. 27, 591–598 (2009).
, http://www.100md.com
[5] Abali H, Disel U, Köse F et al. Immediate or delayed docetaxel: does progression-free survival really reflect two strategies? J. Clin. Oncol. 27(17), 2889 (2009).
[6] Ciuleanu T, Brodowicz T, Zielinski et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non small cell lung cancer: a randomized, double blind, Phase 3 study. Lancet 374, 1432–1440 (2009).
[7] Peterson P, Park K, Fossella F et al. Is pemetrexed more effective in adenocarcinoma and large cell lung cancer than in squamous cell carcinoma? A retrospective analysis of a Phase III trial of pemetrexed vs docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC): P2-328. J. Thorac. Oncol. 2(Suppl. 4), s851 (2007).
, 百拇医药
[8] Scagliotti GV, Parikh P, von Pawel J et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy naive patients with advanced stage non-small-cell lung cancer. J. Clin. Oncol. 26, 3543–3551 (2008).
[9] Brugger W, Kim J-H, Hansen O et al. Biomarker analyses from SATURN a Phase III placebo controlled study of erlotinib as first line maintenance therapy for advanced NSCLC. Eur. J. Cancer 7(2 Suppl.), 559, (2009) (Abstract 9176).
, http://www.100md.com
[10]Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 361(10), 947–957 (2009).
[11]Pirker R, Pereira JR, Szczesna A et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised Phase III trial. Lancet 373(9674), 1525–1531 (2009)., http://www.100md.com(张春玲 刘凤娟)