TY - JOUR
T1 - Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer
T2 - a phase III randomised controlled trial
AU - Albain, Kathy S.
AU - Swann, R. Suzanne
AU - Rusch, Valerie W.
AU - Turrisi, Andrew T.
AU - Shepherd, Frances A.
AU - Smith, Colum
AU - Chen, Yuhchyau
AU - Livingston, Robert B.
AU - Feins, Richard H.
AU - Gandara, David R.
AU - Fry, Willard A.
AU - Darling, Gail
AU - Johnson, David H.
AU - Green, Mark R.
AU - Miller, Robert C.
AU - Ley, Joanne
AU - Sause, Willliam T.
AU - Cox, James D.
N1 - Funding Information:
This trial was funded by the National Cancer Institute (PHS Cooperative Agreement grant numbers CA21661, CA37422, CA32115, CA46441, CA77202, CA49957, CA03927, CA25224) with high priority designation, and Canadian Cancer Society (NCIC10362), and administered by the Radiation Therapy Oncology Group (RTOG, R9309), with participation by Southwest Oncology Group, National Cancer Institute of Canada Clinical Trials Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, and North Central Cancer Treatment Group. We thank the many North American Intergroup discipline chairs and others who provided advice or assistance during the design of this study or while the study was in progress; the members of the Lung Cancer Committees of the Southwest Oncology Group, National Cancer Institute of Canada Clinical Trials Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, and the North Central Cancer Treatment Group for their support of this study over the long accrual period; and especially the lung cancer survivors who were treated and followed up on this protocol, and the lay advocates who supported this trial design.
PY - 2009/8/7
Y1 - 2009/8/7
N2 - Background: 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. Methods: 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/m2 on days 1, 8, 29, and 36] and etoposide [50 mg/m2 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. Findings: 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. Interpretation: Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patients with stage IIIA(N2) non-small-cell lung cancer. Funding: National Cancer Institute, Canadian Cancer Society, and National Cancer Institute of Canada.
AB - Background: 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. Methods: 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/m2 on days 1, 8, 29, and 36] and etoposide [50 mg/m2 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. Findings: 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. Interpretation: Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patients with stage IIIA(N2) non-small-cell lung cancer. Funding: National Cancer Institute, Canadian Cancer Society, and National Cancer Institute of Canada.
UR - http://www.scopus.com/inward/record.url?scp=67651241508&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67651241508&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(09)60737-6
DO - 10.1016/S0140-6736(09)60737-6
M3 - Article
C2 - 19632716
AN - SCOPUS:67651241508
SN - 0140-6736
VL - 374
SP - 379
EP - 386
JO - The Lancet
JF - The Lancet
IS - 9687
ER -