Zalcman G, Richard N, Bergot E
Service de Pneumologie, UFR de Médecine Caen-Basse Normandie, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen Cedex 05.
Rev Pneumol Clin. 2007 Feb;63(1):20-8. doi: 10.1016/s0761-8417(07)90085-1.
Therapies targeted on cell signal pathways that control cell division and tumor angiogenesis have been developed over the last five years for non small cell lung cancer (NSCLC) with some amazing results, in subgroups of selected patients, predicting more significant success in the upcoming years. Compounds targeted on EGF tyrosine kinase receptor have been tested in large clinical phase 2 and 3 trials including thousands of patients. Their efficacy has been proved, in second and third line trials, after first line cisplatin-based chemotherapy for non-mucinous adenocarcinoma in non-smokers, women and Asian patients. Response rates vary from 10% in non selected Caucasian patients to 40% in non-smoking Asian patients with long survivals. Therapeutic targeting improves success rates, either relying on EGFR gene amplification detection by FISH, or search for EGFR tyrosine kinase domain mutations. Commercial kits are available for routine molecular diagnosis of domain mutations potentially enabling molecular targeting in addition to clinical targeting. Angiogenesis inhibitors, especially monoclonal antibody to VEGF, bevacizumab, have also been developed in the last few years. Bevacizumab associated with classical cytotoxic chemotherapy led, in selected patients (with non squamous cell lung cancer and no past history of cardiovascular disease) to an increase of median survival to more than 12 months with tolerable toxicity. Other drugs that have both anti-EGFR activity and anti-angiogenic properties will be soon developed, since future bioactive anti-cancer drugs will probably be multi-targeted drugs.
在过去五年中,针对控制细胞分裂和肿瘤血管生成的细胞信号通路开发了多种疗法,用于治疗非小细胞肺癌(NSCLC),并取得了一些惊人的成果。在部分选定患者亚组中,这些疗法显示出显著效果,预示着未来几年将取得更大成功。针对表皮生长因子(EGF)酪氨酸激酶受体的化合物已在包含数千名患者的大型临床2期和3期试验中进行了测试。在针对非吸烟患者、女性患者及亚洲患者的非黏液腺癌进行一线顺铂化疗后的二线和三线试验中,其疗效得到了证实。缓解率从非选定白种人患者的10%到长期存活的非吸烟亚洲患者的40%不等。治疗靶向提高了成功率,这既可以依靠荧光原位杂交(FISH)检测表皮生长因子受体(EGFR)基因扩增,也可以通过寻找EGFR酪氨酸激酶结构域突变来实现。目前已有商业试剂盒可用于常规分子诊断结构域突变,这除了临床靶向之外还可能实现分子靶向。血管生成抑制剂,特别是针对血管内皮生长因子(VEGF)的单克隆抗体贝伐单抗,也在过去几年中得到了开发。在选定患者(非鳞状细胞肺癌且无心血管疾病病史)中,贝伐单抗与传统细胞毒性化疗联合使用可使中位生存期延长至12个月以上,且毒性可耐受。由于未来的生物活性抗癌药物可能是多靶点药物,因此兼具抗EGFR活性和抗血管生成特性的其他药物也将很快被开发出来。