1、从临床试验看非小细胞肺癌的化疗进展Braverilee 综述 张湘茹 孙燕 审校 （中国医学科学院 中国协和医科大学 肿瘤医院内科，北京 100021） 概述非小细胞肺癌（NSCLC）占癌症发病率的 13，癌症死亡率的 17.8%，总体五年生存率 15。NSCLC 的发病率在大多数国家明显上升，男性肿瘤中肺癌居首位，女性居第二、三位，占癌症总死亡率的 1/3，死亡人数较乳腺癌、前列腺癌和结肠癌的总和还多，80-90%的肺癌病人最终死于肺癌。在美国每年新肺癌发病例数约 172,000，已达发病的平台期，但我国近 30 年发病率明显上升，尤在大城市和工矿地区。NSCLC 的发病率占肺癌80，2/3
2、 的病人确诊时巳失去手术机会，即为 b-期患者，其中位生存期仅为 5-10 个月，几乎不可治愈，此时，首选的治疗为全身化疗。和最佳支持治疗（BSC）相比，化疗能延长患者生存期，改善症状，提高生活质量。以烷化剂为基础的第一代化疗方案（CTX、IFO、CCNU、ADM ）对肺癌的近期疗效好于最佳支持治疗，但远期作用微乎其微，甚或有害。70 年代以来，铂类在治疗晚期 NSCLC中占有重要地位，研究表明，植物碱类为代表的二代化疗药物（VDS、MMC、VP16）联合铂类化疗较单用铂类有效性明显提高。NSCLC 治疗协作组研究证实以铂类为基础的化疗可提高肺癌患者 5 年生存率 5，并且能提高患者的生活质量
3、（QOL） ，缓解症状。随着化疗的发展，90 年代逐渐出现了 DOC、PTX、NVB、GEM、CPT-11 等新一代治疗非小细胞肺癌的化学药物。这些药物治疗 NSCLC 的单药活性都在 15以上，由这些药物组成的各种化疗方案已广泛应用于临床，并取得了良好的效果。DOC、PTX、NVB、GEM 与CBP 或 DDP 联合方案中，有效率约为 20-50%，有效率几乎是旧的含铂化疗方案的 2 倍。各新药与铂类组成的方案间，毒副反应各异，疗效相似，耐受性尚好。因此，这些化疗方案治疗晚期 NSCLC 得到广泛认可，第三代含铂双药方案已成为当今治疗转移性 NSCLC的标准方案。二新药联合铂类与一新药联合铂
4、类方案比较，疗效相似,但毒性增加。但即使这些药物联合治疗肺癌，中位生存期也仅仅为 8-11 月，1 年和 2 年的生存率分别为 35%和10-15%，一旦进展，BSC 的中位生存期仅为 4.6 月，很明显需要新的治疗方案。目前，手术、放疗和化疗对 NSCLC 作用有限。20 年来，肺癌在筛查、预防和治疗上进展也显缓慢，给予厚望的靶向治疗亦并不近人意，如 gefitinib 单药治疗 NSCLC 的IDEAL1、IDEAL2 及 ISEL 试验阴性，gefitinib 联合化疗的 INTACT1、INTACT2 试验阴性，erlotinib 联合化疗的 TALENT、TRIBUTE 试验阴性，B
5、exarotene 联合化疗的SPIRIT1、SPIRIT2 试验阴性， Marimastat 维持治疗阴性、Lonafarnib 联合化疗亦为阴性，胸部 X 线筛查试验阴性， -carotene/retinol 的、级化学预防试验阴性。尽管如此，靶向治疗仍不乏闪光之处，如 gefitinib、erlotinib 对东方人、腺癌、不吸烟者疗效较好，Bexarotene 联合化疗对高三酯血症患者疗效好，尚可延长其生存。本文就 NSCLC 辅助、新辅助化疗、一线、二线化疗、老年或行为状态差的患者化疗、靶向治疗以及肺泡癌的治疗进展做一综述。 非小细胞肺癌的辅助化疗NSCLC 即使是早期，对很大程度的
6、部分病人来说依然是致命性的，标准的治疗取决于病人是否能够耐受手术，手术治疗 B 病人 5 年生存率为 57，期患者小于 50。约1/3 的早期 NSCLC 患者术后复发，远处转移是其死亡的主要原因。为减少局部复发和远处转移，术后辅助化疗和/或放疗显得尤为关注，但一项 meta 分析表明，根治性术后放疗（普放）对早期肺癌的生存是有害的 1 。最初的化疗结果也令人沮丧，以至很长的一段时间认为手术是其标准的治疗策略。但 1995 年一项汇聚了 52 个随机临床研究试验的 NSCLC Collaborative Group 的 meta 分析表明，术后铂类为主的辅助化疗可以改善 5 年生存率5 2 ，
7、尽管数字较小，甚至并未达到统计学意义（p0.08） ，但极大地鼓舞了研究者对辅助化疗的信心，但另一方面，该 meta 分析表明以烷化剂为基础的方案降低 5 年生存率5。随着新一代化疗药物的不断涌现，辅助化疗也在不断的取得进展，越来越多辅助化疗的阳性结果也逐渐更新了临床医生，特别是外科医生对 NSCLC 化疗的认识。表 1 列举了肺癌辅助化疗试验结果。表 1 非小细胞肺癌辅助化疗结果作者年月 病例数 期别 治疗 5-年生存率P 值 HR 结果Waller BLT 20033381 - VdsP 或 MIC 或MVC 或 NP1.02 Scagliotti ALPI 200341,209 -a M
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