Faculty Collaboration Database

Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst 2011 Oct 05;103(19):1452-60

Date

09/10/2011

Pubmed ID

21903745

Pubmed Central ID

PMC3186782

DOI

10.1093/jnci/djr325

Scopus ID

2-s2.0-80054072961 (requires institutional sign-in at Scopus site)   1011 Citations

Abstract

BACKGROUND: The combination of chemotherapy with thoracic radiotherapy (TRT) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non-small cell lung cancer. However, it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy.

METHODS: A total of 610 patients were randomly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial. The sequential arm included cisplatin at 100 mg/m2 on days 1 and 29 and vinblastine at 5 mg/m2 per week for 5 weeks with 63 Gy TRT delivered as once-daily fractions beginning on day 50. Arm 2 used the same chemotherapy regimen as arm 1 with 63 Gy TRT delivered as once-daily fractions beginning on day 1 [corrected]. Arm 3 used cisplatin at 50 mg/m2 on days 1, 8, 29, and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1, 2, 5, and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1. The primary endpoint was overall survival, and secondary endpoints included tumor response and time to tumor progression. Kaplan-Meier analyses were used to assess survival, and toxic effects were examined using the Wilcoxon rank sum test. All statistical tests were two-sided.

RESULTS: Median survival times were 14.6, 17.0, and 15.6 months for arms 1-3, respectively. Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment (5-year survival: sequential, arm 1, 10% [20 patients], 95% confidence interval [CI] = 7% to 15%; concurrent, arm 2, 16% [31 patients], 95% CI = 11% to 22%, P = .046; concurrent, arm 3, 13% [22 patients], 95% CI = 9% to 18%). With a median follow-up time of 11 years, the rates of acute grade 3-5 nonhematologic toxic effects were higher with concurrent than sequential therapy, but late toxic effects were similar.

CONCLUSION: Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies.

Author List

Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD

Author

Elizabeth M. Gore MD Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Canada
Carcinoma, Non-Small-Cell Lung
Chemotherapy, Adjuvant
Cisplatin
Disease Progression
Drug Administration Schedule
Etoposide
Follow-Up Studies
Humans
Kaplan-Meier Estimate
Lung Neoplasms
Male
Middle Aged
Multivariate Analysis
Neoplasm Staging
Odds Ratio
Radiotherapy Dosage
Radiotherapy, Adjuvant
Time Factors
Treatment Outcome
United States
Vinblastine