ⅢA-N_2期非小细胞肺癌术后化疗随机对照研究结果

A prospective randomized study of adjuvant chemotherapy in completely resected stage ⅢA-N2 non-small cell lung cancer

背景与目的 法国的IALT（International Adjuvant Lung Cancer Trial）显示术后辅助化疗使非小细胞肺癌（NSCLC）患者5年生存率提高5％，加拿大的JBR10和美国的CALGB9633的结果提示第三代化疗药物能进一步提高早期（ⅠB～ⅡB期）NSCLC术后的疗效。本研究的目的是探讨术后化疗对完全性切除术后ⅢA-N2期NSCLC患者生存期的影响。方法 1999年1月1日至2003年12月31日，术后确诊为ⅢA—N2期NSCLC患者150例，随机分为术后化疗组（79例）与单纯手术组（71例）。术后化疗组的患者接受长春瑞滨或紫杉醇＋卡铂化疗，每3周一次，共4周期。结果 术后化疗组86．1％（68／79）的患者接受了4个周期的化疗，没有患者死于与化疗相关的毒性作用。25％的患者出现Ⅲ～Ⅳ度白细胞减少，2％的患者出现发热型白细胞减少，恶心、呕吐的发生率分别为56％、35％。全组中位生存期为879天，1年、2年、3年总生存率为81％、59％、43％；无瘤中位生存期为620天，1年、2年、3年无瘤生存率为63％、45％、25％。术后化疗组中位生存期为897天，单纯手术组为821天（P=0．0527）；术后化疗组1年、2年、3年生存率分别为94．71％、76．28％、49．62％，单纯手术组分别为88．24％、60．13％、43．73％，其中1年、2年生存率的差异有统计学意义（z值分别为1．956、2．427，P均＜0．05）。脑转移为最常见的首发转移部位，占26．0％（39／150），其中术后化疗组为22．8％（18／79），单纯手术组为29．6％（21／71）（P〉0．05）。术后化疗组与单纯手术组中脑转移患者的中位生存期分别为812天、512天（P=0．122），2年生存率分别为66．7％、37．6％（P〈0．01）。全组出现脑转移后的中位生存期为190天。结论 ①术后化疗虽不能显著延长ⅢA—N2期NSCLC患者的中位生存期，但显著提高了1年、2年生存率。②术后化疗没有减少ⅢA-N2期NSCLC患者脑转移的发生率，但推迟了脑转移发生的时间。

Background and objective Recently, results from IALT, JBR10 and CALGB9633 showed that postoperative adjuvant chemotherapy improved survival rate of patients with non small cell lung cancer （NSCLC） after complete resection. The aim of this study is to evaluate the effect of postoperative adjuvant chemotherapy on survival after complete resection for stage Ⅲ A N2 NSCLC. Methods From Jan 1999 to Dec 2003, one hundred and fifty patients with stage Ⅲ A N2 NSCLC were randomly divided into two groups. The chemotherapy group received four cycles of chemotherapy with navelbine or paelitaxel plus carboplatin, while the observation group did not receive chemotherapy after operation. Results In the chemotherapy group, 86. 1%（68/79） of patients finished 4 cycles of chemotherapy, and no one died of toxic effects of ehemothera py; 25% of patients had grade Ⅲ-Ⅳ leukopenia, 2% of patients had febrile leukopenia. The median survival time for the entire 150 patients was 879 days, and 1-, 2 and 3-year survival rate was 81%, 59% and 43%. There was no significant difference in median survival between the chemotherapy and observation groups （P 0.0527）. but there was significant difference in the 1- and 2-year survival rate （94. 71% and 76. 28% vs 88.24% and 60. 13%, P〈0. 05）. The most common site of recurrence was the brain. Twenty-six percent （39/150） of patients recurred in the brain as their first site of failure, and 22.8% （18/79） for the chemothera py group, 29.6% （21/71） for the observation group. The median survival time for patients who developed brain metastasis was not significantly different between the chemotherapy and observation groups （812 days vs 512 days, P=0. 122）, but there was significant difference in the 2-year survival rate （66.7% vs 37.6 %, P〈0.01）. The median survival was 190 days for the patients since brain metastasis appeared. Conclusion Postoperative adjuvant chemotherapy dose not significantly improve median survival among patients with completely resected stage Ⅲ A-N2 NSCLC, but significantly improves the 1- and 2-year survival rate. It also dose not decrease the incidence of brain metastasis but puts off the time of brain metastasis.