Vilmar Adam, Sørensen Jens Benn
Department of Oncology 5073, Finsen Centre, National University Hospital, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.
Lung Cancer. 2009 May;64(2):131-9. doi: 10.1016/j.lungcan.2008.08.006. Epub 2008 Sep 19.
Patients diagnosed with advanced non-small cell lung cancer have a dismal prognosis and are often relative resistant to chemotherapy. A need for markers has emerged based on tumour biology in order to predict which patients will respond to treatment. Excision repair cross-complementation group 1 (ERCC1) has shown potential as a predictive marker in patients with NSCLC treated with cisplatin-based chemotherapy. Carboplatin has gained widespread use in the treatment of advanced NSCLC and its mechanisms of action are likely similar to that of cisplatin.
A literature review on ERCC1 was conducted as predictor in NSCLC patients receiving platinum-based treatment with emphasis on carboplatin. English language publications from January 1996 to February 2008 were eligible and data on methodology and outcome were recorded.
Eight preclinical articles, 25 clinical articles and 1 clinical abstract were identified. Laboratory methods were mainly RT-PCR (reverse transcriptase polymerase chain reaction) or immunohistochemistry (IHC) for expression of ERCC1. Preclinical studies pointed towards similar mechanisms of chemotherapy-resistance among platinum compounds. A statistically significant benefit in outcome was found among NSCLC patients, who received adjuvant treatment, and had low-ERCC1 expression. Advanced NSCLC patients treated with cisplatin showed improved response rates (RR) but no difference in other endpoints. Studies on advanced NSCLC patients treated with carboplatin were sparse, heterogeneous and small thus reporting varying results.
The literature on advanced NSCLC patients treated with carboplatin or cisplatin are dominated by small and heterogeneous patient populations and yielded different results. No firm conclusions can be drawn on carboplatin based on the current literature. Research on the development of a reliable methodology is warranted followed by validation in large, prospective, randomized trials as ERCC1 may possibly play an important role as tumour marker in tailored chemotherapy for NSCLC.
被诊断为晚期非小细胞肺癌的患者预后不佳,且通常对化疗相对耐药。基于肿瘤生物学,人们对能够预测哪些患者会对治疗产生反应的标志物的需求日益凸显。切除修复交叉互补基因1(ERCC1)已显示出作为接受铂类化疗的非小细胞肺癌患者预测标志物的潜力。卡铂已广泛应用于晚期非小细胞肺癌的治疗,其作用机制可能与顺铂相似。
对ERCC1作为接受铂类治疗的非小细胞肺癌患者预测指标进行文献综述,重点关注卡铂。纳入1996年1月至2008年2月的英文出版物,并记录方法和结果数据。
共识别出8篇临床前文章、25篇临床文章和1篇临床摘要。实验室方法主要是用于检测ERCC1表达的逆转录聚合酶链反应(RT-PCR)或免疫组织化学(IHC)。临床前研究表明铂类化合物之间存在相似的化疗耐药机制。在接受辅助治疗且ERCC1表达低的非小细胞肺癌患者中,发现结局有统计学意义的改善。接受顺铂治疗的晚期非小细胞肺癌患者显示出缓解率(RR)提高,但在其他终点上无差异。关于接受卡铂治疗的晚期非小细胞肺癌患者的研究较少、异质性大且样本量小,因此结果各异。
关于接受卡铂或顺铂治疗的晚期非小细胞肺癌患者的文献主要是小样本且异质性大的患者群体,结果各异。基于当前文献,无法对卡铂得出确凿结论。鉴于ERCC1可能在非小细胞肺癌的个体化化疗中作为肿瘤标志物发挥重要作用,有必要开展关于开发可靠方法的研究,随后在大型前瞻性随机试验中进行验证。