Department of Clinical and Biological Sciences, University of Turin, Thoracic Oncology Unit, San Luigi Hospital, Orbassano, Turin, Italy.
Oncology (Williston Park). 2009 Nov 30;23(13):1133-40.
Platinum-based doublet chemotherapy remains the cornerstone of therapy in the first-line setting in advanced non-small-cell lung cancer (NSCLC) for patients with good performance status. However, this paradigm has recently been challenged by the results of a study that showed a survival benefit with the addition of bevacizumab to carboplatin and paclitaxel in bevacizumab-eligible patients and by the superior efficacy of gefitinib and erlotinib compared to chemotherapy in epidermal growth factor receptor (EGFR) gene mutation-positive tumors (mainly adenocarcinomas). In addition, histology has been recently recognized as a potential predictive factor in advanced NSCLC patients treated with chemotherapy. Prospective data from a preplanned subgroup analysis of a phase III study and retrospective reviews consistently reported a significant interaction between treatment by histology and response/survival in nonsquamous NSCLCs treated with pemetrexed, compared to squamous cell carcinoma (SCC). Thymidylate synthase, the main target of pemetrexed, was found to be differentially expressed among the histotypes of lung cancer, being lower in adenocarcinoma and higher in SCC and small-cell lung cancer. Thus, the availability of adequate amounts of tissue from biopsies to allow accurate pathologic subclassifications at diagnosis will be critical to help the oncologist select the most appropriate chemotherapy regimen as we move toward an individualized molecularly based approach.
铂类双联化疗仍然是具有良好体能状态的晚期非小细胞肺癌（NSCLC）患者一线治疗的基石。然而，最近的一项研究结果对这一模式提出了挑战，该研究表明在贝伐珠单抗适用的患者中，贝伐珠单抗联合卡铂和紫杉醇可带来生存获益，而且与化疗相比，吉非替尼和厄洛替尼在表皮生长因子受体（EGFR）基因突变阳性肿瘤（主要为腺癌）中具有更好的疗效。此外，组织学最近被认为是接受化疗的晚期 NSCLC 患者的一个潜在预测因素。III 期研究的一项预先计划的亚组分析的前瞻性数据和回顾性综述一致报告，与鳞癌（SCC）相比，培美曲塞治疗的非鳞 NSCLC 中，治疗方法与反应/生存之间存在显著的交互作用。胸苷酸合成酶是培美曲塞的主要靶点，在肺癌的组织学类型中存在差异表达，在腺癌中表达较低，在 SCC 和小细胞肺癌中表达较高。因此，在向个体化的基于分子的方法转变时，为了帮助肿瘤学家选择最合适的化疗方案，从活检中获得足够数量的组织以进行准确的病理亚型分类将是至关重要的。
