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 Methods: Eligible patients were treatment naive, and had stage IIIA and B unresectable non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and normal organ function. 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 months 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) or 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, and 24% and 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 advantage with the HART regimen.