Gilligan David, Nicolson Marianne, Smith Ian, Groen Harry, Dalesio Otilia, Goldstraw Peter, Hatton Matthew, Hopwood Penelope, Manegold Christian, Schramel Franz, Smit Hans, van Meerbeeck Jan, Nankivell Matthew, Parmar Mahesh, Pugh Cheryl, Stephens Richard
Addenbrooke's Hospital, Cambridge, UK.
Lancet. 2007 Jun 9;369(9577):1929-37. doi: 10.1016/S0140-6736(07)60714-4.
Although surgery offers the best chance of cure for patients with non-small cell lung cancer (NSCLC), the overall 5-year survival rate is modest, and improvements are urgently needed. In the 1990s, much interest was generated from two small trials that reported striking results with neo-adjuvant chemotherapy, and therefore our intergroup randomised trial was designed to investigate whether, in patients with operable non-small cell lung cancer of any stage, outcomes could be improved by giving platinum-based chemotherapy before surgery.
Patients were randomised to receive either surgery alone (S), or three cycles of platinum-based chemotherapy followed by surgery (CT-S). Before randomisation, clinicians chose the chemotherapy that would be given from a list of six standard regimens. The primary outcome measure was overall survival, which was analysed on an intention-to-treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN25582437.
519 patients were randomised (S: 261, CT-S: 258) from 70 centres in the UK, Netherlands, Germany, and Belgium. Most (61%) were clinical stage I, with 31% stage II, and 7% stage III. Neo-adjuvant chemotherapy was feasible (75% of patients received all three cycles of chemotherapy), resulted in a good response rate (49% [95% CI 43%-55%]) and down-staging in 31% (25%-37%) of patients, and did not alter the type or completeness of the surgery (lobectomy: S: 56%, CT-S: 60%, complete resection: S: 80%, CT-S: 82%). Post-operative complications were not increased in the CT-S group, and no impairment of quality of life was observed. However, there was no evidence of a benefit in terms of overall survival (hazard ratio [HR] 1.02, 95% CI 0.80-1.31, p=0.86). Updating the systematic review by addition of the present result suggests a 12% relative survival benefit with the addition of neoadjuvant chemotherapy (1507 patients, HR 0.88, 95% CI 0.76-1.01, p=0.07), equivalent to an absolute improvement in survival of 5% at 5 years
Although there was no evidence of a difference in overall survival with neo-adjuvant chemotherapy, the result is statistically consistent with previous trials, and therefore adds considerable weight to the current evidence.
尽管手术为非小细胞肺癌（NSCLC）患者提供了最佳的治愈机会，但总体5年生存率并不理想，迫切需要改善。在20世纪90年代，两项小型试验报告了新辅助化疗的显著效果，引发了广泛关注。因此，我们的组间随机试验旨在研究，对于任何分期的可手术非小细胞肺癌患者，术前给予铂类化疗是否能改善预后。
患者被随机分为两组，一组仅接受手术（S），另一组接受三个周期的铂类化疗后再进行手术（CT-S）。在随机分组前，临床医生从六种标准方案中选择化疗方案。主要结局指标是总生存期，采用意向性分析。本研究已注册为国际标准随机对照试验，注册号为ISRCTN25582437。
来自英国、荷兰、德国和比利时70个中心的519例患者被随机分组（S组：261例，CT-S组：258例）。大多数患者（61%）为临床I期，31%为II期，7%为III期。新辅助化疗是可行的（75%的患者接受了全部三个周期的化疗），有效率良好（49%[95%CI 43%-55%]），31%（25%-37%）的患者分期降低，且未改变手术类型或切除完整性（肺叶切除术：S组56%，CT-S组60%；完全切除：S组80%，CT-S组82%）。CT-S组术后并发症未增加，且未观察到生活质量受损。然而，在总生存期方面没有获益的证据（风险比[HR]1.02，95%CI 0.80-1.31，p=0.86）。将本研究结果纳入系统评价后更新的数据表明，新辅助化疗可使相对生存率提高12%（1507例患者，HR 0.88，95%CI 0.76-1.01，p=0.07），相当于5年生存率绝对提高5%。
尽管新辅助化疗在总生存期方面没有差异的证据，但该结果在统计学上与先前试验一致，因此为当前证据增添了相当大的分量。
