Albain Kathy S, Swann R Suzanne, Rusch Valerie W, Turrisi Andrew T, Shepherd Frances A, Smith Colum, Chen Yuhchyau, Livingston Robert B, Feins Richard H, Gandara David R, Fry Willard A, Darling Gail, Johnson David H, Green Mark R, Miller Robert C, Ley Joanne, Sause Willliam T, Cox James D
Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153-5589, USA.
Lancet. 2009 Aug 1;374(9687):379-86. doi: 10.1016/S0140-6736(09)60737-6. Epub 2009 Jul 24.
Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases (N2) have shown the feasibility of resection after concurrent chemotherapy and radiotherapy with promising rates of survival. We therefore did this phase III trial to compare concurrent chemotherapy and radiotherapy followed by resection with standard concurrent chemotherapy and definitive radiotherapy without resection.
Patients with stage T1-3pN2M0 non-small-cell lung cancer were randomly assigned in a 1:1 ratio to concurrent induction chemotherapy (two cycles of cisplatin [50 mg/m(2) on days 1, 8, 29, and 36] and etoposide [50 mg/m(2) on days 1-5 and 29-33]) plus radiotherapy (45 Gy) in multiple academic and community hospitals. If no progression, patients in group 1 underwent resection and those in group 2 continued radiotherapy uninterrupted up to 61 Gy. Two additional cycles of cisplatin and etoposide were given in both groups. The primary endpoint was overall survival (OS). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00002550.
202 patients (median age 59 years, range 31-77) were assigned to group 1 and 194 (61 years, 32-78) to group 2. Median OS was 23.6 months (IQR 9.0-not reached) in group 1 versus 22.2 months (9.4-52.7) in group 2 (hazard ratio [HR] 0.87 [0.70-1.10]; p=0.24). Number of patients alive at 5 years was 37 (point estimate 27%) in group 1 and 24 (point estimate 20%) in group 2 (odds ratio 0.63 [0.36-1.10]; p=0.10). With N0 status at thoracotomy, the median OS was 34.4 months (IQR 15.7-not reached; 19 [point estimate 41%] patients alive at 5 years). Progression-free survival (PFS) was better in group 1 than in group 2, median 12.8 months (5.3-42.2) vs 10.5 months (4.8-20.6), HR 0.77 [0.62-0.96]; p=0.017); the number of patients without disease progression at 5 years was 32 (point estimate 22%) versus 13 (point estimate 11%), respectively. Neutropenia and oesophagitis were the main grade 3 or 4 toxicities associated with chemotherapy plus radiotherapy in group 1 (77 [38%] and 20 [10%], respectively) and group 2 (80 [41%] and 44 [23%], respectively). In group 1, 16 (8%) deaths were treatment related versus four (2%) in group 2. In an exploratory analysis, OS was improved for patients who underwent lobectomy, but not pneumonectomy, versus chemotherapy plus radiotherapy.
Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patients with stage IIIA(N2) non-small-cell lung cancer.
National Cancer Institute, Canadian Cancer Society, and National Cancer Institute of Canada.
针对伴有同侧纵隔淋巴结转移（N2）的IIIA期非小细胞肺癌患者的II期研究结果显示，同步放化疗后进行手术切除具有可行性，生存率前景可观。因此，我们开展了这项III期试验，以比较同步放化疗后行手术切除与单纯同步放化疗（不行手术切除）的疗效。
T1-3pN2M0期非小细胞肺癌患者按1:1比例随机分配至多家学术及社区医院，接受同步诱导化疗（顺铂[第1、8、29和36天50mg/m²]和依托泊苷[第1 - 5天和29 - 33天50mg/m²]两个周期）加放疗（45Gy）。若病情无进展，1组患者接受手术切除，2组患者继续不间断放疗直至61Gy。两组均追加顺铂和依托泊苷两个周期。主要终点为总生存期（OS）。分析采用意向性分析。本研究已在ClinicalTrials.gov注册，编号为NCT00002550。
202例患者（中位年龄59岁，范围31 - 77岁）被分配至1组，194例（61岁，32 - 78岁）被分配至2组。1组中位OS为23.6个月（IQR 9.0 - 未达到），2组为22.2个月（9.4 - 52.7）（风险比[HR] 为0.87 [0.70 - 1.10]；p = 0.24）。1组5年存活患者数为37例（点估计值27%），2组为24例（点估计值20%）（优势比0.63 [0.36 - 1.10]；p = 0.10）。开胸手术时N0状态下，中位OS为34.4个月（IQR 15.7 - 未达到；19例[点估计值41%]患者5年存活）。1组无进展生存期（PFS）优于2组，中位分别为12.8个月（5.3 - 42.2）和10.5个月（4.8 - 20.6），HR 0.77 [0.62 - 0.96]；p = 0.017）；5年无疾病进展患者数分别为32例（点估计值22%）和13例（点估计值11%）。中性粒细胞减少和食管炎是1组（分别为77例[38%]和20例[10%]）及2组（分别为80例[41%]和44例[23%]）同步放化疗相关的主要3级或4级毒性反应。1组有16例（8%）死亡与治疗相关，2组有4例（2%）。在一项探索性分析中，与同步放化疗相比，接受肺叶切除术而非全肺切除术的患者OS有所改善。
对于IIIA（N2）期非小细胞肺癌患者，同步放化疗联合或不联合手术切除（最好是肺叶切除术）都是可行的治疗选择。
美国国立癌症研究所、加拿大癌症协会和加拿大国立癌症研究所。
