Phase III study of the eastern cooperative oncology group (ECOG 2597): Induction chemotherapy followed by either standard thoracic radiotherapy or hyperfractionated accelerated radiotherapy for patients with unresectable stage IIIA and B non-small-cell lung cancer

Purpose To compare once-daily radiation therapy (qdRT) with hyperfractionated accelerated radiation therapy (HART) after two cycles of induction chemotherapy. Patients and Mehtods Eligible patients were treaatment naive, and has stage IIA and B unrresectable non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and normal organ functio. Induction chemotherapy consisted of two cycles of carboplatin area under time-concentration curve 6 mg/mL (.) min plus paclitaxel 225 mg/m(2) on day 1. RT consisted of arm 1 (qdRT), 64 Gy (2 Gy/d), versus arm 2 (HART), 57.6 Gy (1.5 Gy tid for 2.5 weeks). A total of 388 patients were needed to detect a 50% increase in median survival from 14 months of qdRT to 21 onths of HART; accrual was not achieved and the study closed prematurely. Results Of 141 patients enrolled, 83% were randomly assigned after chemotherapy to qdRT (n = 59) of HART (n = 60). Median survival was 20.3 and 14.9 months for HART and qdRT, respectively ( P = .28). Overall response was 25% and 22% for HART and qdRT respectively (P = .69). Two- and 3-year survival was 44% and 34% for HART anf 24% amd 14% for qdRT, respectively. Grade >= 3 toxicities included esophagitis in 14 v nine patients and pneumonitis in 0 v 6 patients for HART and qdRT, respectively. Any subsequent trials of the HART regimen must address the issues that led to early closure, including slow accrual, logistics of HART, mucosal toxicity, and the fact that concurrent chemoradiotherapy now seems more effective than sequential treatment. Conclusion After two cycles of induction chemotherapy with carboplatin-paclitaxel, HART is feasible with an acceptable toxicity profile. Although statistical significance was not achieved and the study closed early, there was a positive statistical trend suggesting a survival advantge with the HART regime. (c) 2005 by American Society of Clinical Oncology.