US Oncology, 10101 Woodloch Forest, The Woodlands, TX 77380, USA.
Am J Health Syst Pharm. 2010 Jan 1;67(1 Suppl 1):S9-14. doi: 10.2146/ajhp090457.
To review recent clinical trials that have examined new options for the treatment of non-small-cell lung cancer (NSCLC) and to review the importance of tumor histology and genetics in the selection of therapy.
Targeted biological agents have been evaluated for use in patients with NSCLC. In a recent study, treatment with cetuximab plus chemotherapy led to significant improvement in overall survival (OS) in patients with advanced NSCLC. A Phase III, noninferiority, randomized study evaluating first-line therapy in patients with stage IIIb or IV NSCLC demonstrated that the combination of cisplatin and pemetrexed was noninferior to cisplatin and gemcitabine in improving OS and other clinical outcomes. In this study, the combination of pemetrexed and cisplatin was effective in patients with nonsquamous disease, whereas the combination of cisplatin and gemcitabine was effective in improving progression-free survival (PFS) in patients with squamous cell carcinoma. Clinical trials of maintenance therapy presented at the 2009 annual meeting of the American Society of Clinical Oncology reported significant benefit of pemetrexed in patients with nonsquamous tumor histology, and of erlotinib in patients with squamous and nonsquamous histology. For second-line therapy, studies of the investigational tyrosine kinase inhibitor, vandetanib, failed to demonstrate improved OS with vandetanib in combination with docetaxel or pemetrexed, or in direct comparison with erlotinib. In another study, the addition of bevacizumab to erlotinib for second-line treatment of NSCLC did not result in greater OS than erlotinib alone.
New treatment strategies are needed to improve clinical outcomes for patients with advanced NSCLC. The introduction of new agents with improved tolerability profiles has led to interest in long-term maintenance therapy in this patient population. Clinical trials suggest that tumor histology and genetics should be considered when selecting treatments for these patients.
回顾近期有关非小细胞肺癌（NSCLC）治疗新选择的临床试验，并探讨肿瘤组织学和遗传学在治疗选择中的重要性。
已评估靶向生物制剂在 NSCLC 患者中的应用。在最近的一项研究中，西妥昔单抗联合化疗可显著改善晚期 NSCLC 患者的总生存期（OS）。一项 III 期非劣效性、随机研究评估了 IIIB 期或 IV 期 NSCLC 患者的一线治疗，结果表明顺铂联合培美曲塞与顺铂联合吉西他滨在改善 OS 和其他临床结局方面无差异。在这项研究中，培美曲塞联合顺铂对非鳞状疾病患者有效，而顺铂联合吉西他滨可改善鳞状细胞癌患者的无进展生存期（PFS）。在 2009 年美国临床肿瘤学会年会上报告的维持治疗临床试验结果显示，培美曲塞对非鳞状肿瘤组织学患者、厄洛替尼对鳞状和非鳞状组织学患者均有显著获益。对于二线治疗，研究发现，与培美曲塞或多西他赛联合应用或与厄洛替尼直接比较，新型酪氨酸激酶抑制剂凡德他尼联合多西他赛或培美曲塞并不能改善 OS。另一项研究显示，贝伐单抗联合厄洛替尼二线治疗 NSCLC 并不能提高 OS 。
需要新的治疗策略来改善晚期 NSCLC 患者的临床结局。新的药物具有更好的耐受性，因此人们对该患者人群的长期维持治疗产生了兴趣。临床试验提示，在选择这些患者的治疗方法时，应考虑肿瘤组织学和遗传学因素。
