Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
Clin Lung Cancer. 2008 Mar;9 Suppl 2:S76-82. doi: 10.3816/CLC.2008.s.012.
Metastatic non-small-cell lung cancer remains a fatal disease with a median survival of < 1 year. A critical challenge is to develop predictive markers for customizing platinum-based treatment. The first studies focused on the excision repair cross-complementing 1 (ERCC1) gene in this difficult task. Several layers of evidence indicate that ERCC1 mRNA expression could be a predictive marker for cisplatin alone or in combination with certain drugs such as etoposide, gemcitabine, and 5-fluorouracil but not in combination with antimicrotubule drugs. Several retrospective studies demonstrated an impressive survival advantage for gemcitabine plus cisplatin but not for other combinations in tumors with low ERCC1 expression. A customized phase III ERCC1-based trial met the primary endpoint of improvement in response but not in survival, leading us to hypothesize that docetaxel might not be the most appropriate partner for cisplatin in the presence of low ERCC1 levels or for gemcitabine in the presence of high ERCC1 levels. A phase II study demonstrated the feasibility of combining carboplatin, gemcitabine, docetaxel, and vinorelbine according to ERCC1 and ribonucleotide reductase subunit M1 expression levels. These findings highlight the importance of continual learning, and decision-making strategies for customizing treatment should reflect the limitations of our knowledge.
转移性非小细胞肺癌仍然是一种致命疾病，中位生存期<1 年。一个关键的挑战是开发预测标志物，以定制基于铂的治疗方法。最初的研究集中在切除修复交叉互补基因 1（ERCC1）基因上，以完成这一艰巨的任务。有几方面的证据表明，ERCC1 mRNA 表达可以作为预测标志物，用于顺铂单药或与某些药物联合治疗，如依托泊苷、吉西他滨和 5-氟尿嘧啶，但与抗微管药物联合治疗无效。几项回顾性研究表明，在 ERCC1 低表达的肿瘤中，吉西他滨加顺铂联合治疗具有显著的生存优势，但其他联合治疗方案则没有。一项基于 ERCC1 的定制 III 期试验达到了改善反应而不是生存的主要终点，这使我们假设在 ERCC1 水平低的情况下，多西他赛可能不是顺铂的最佳伴侣，而在 ERCC1 水平高的情况下，多西他赛可能不是吉西他滨的最佳伴侣。一项 II 期研究表明，根据 ERCC1 和核糖核苷酸还原酶亚单位 M1 的表达水平，联合使用卡铂、吉西他滨、多西他赛和长春瑞滨是可行的。这些发现强调了不断学习的重要性，并且定制治疗的决策策略应该反映我们知识的局限性。
