Induction chemotherapy with cetuximab, vinorelbine-cisplatin followed by thoracic radiotherapy and concurrent cetuximab, vinorelbine-cisplatin in patients with unresectable stage III non-small cell lung cancer

Objectives: The modest benefits from concurrent chemoradiotherapy(CCRT) in patients with stage III non-small cell lung cancer (NSCLC) warrant a more effective treatment regimen. We herein report mature data of a phase I/II study testing the addition of cetuximab to induction vinorelbine/cisplatin (NP) followed by concurrent cetuximab NP and thoracic radiation in patients with unresectable stage III NSCLC. Materials and Methods: Eligible patients were treated with weekly cetuximab (initial dose 400 mg/m(2), day 1, week 1; maintenance dose 250 mg/m(2) from week 2 to the end of CCRT) and induction vinorelbine (25 mg/m(2), days 1 and 8) and cisplatin (75 mg/m(2), day 1) every 3 weeks for 2 cycles from week 2. Concomitant thoracic radiation (60-66 Gy/2 Gy) and two cycles of NP (vinorelbine 12.5 mg/m(2), days 1 and 8; cisplatin 25 mg/m(2), days 1 to 3, every 3 weeks) were started from week 7. The primary endpoints were toxicities; the secondary endpoints encompassed response rate and survival. Results: In total, 27 patients were enrolled, and 24 completed the full regimen. No treatment-related death occurred. Severe (CTCAE Grade 3 or high) adverse events were experienced by 81% patients (22/27), mostly haematologic. Severe non-haematologic toxicities including nausea/vomiting, intestinal obstruction, pulmonary infection and esophagitis, each of which was detected in <7% of patients. With a median follow-up of 26.7 months, the median survival was 26.7 months, with 1-and 2-year survival rates of 88.9% and 51.9%, respectively. Six patients remained progression-free to date, and the median progression-free survival was 13.5 months. The overall response rate was 63% and 77.8% after the induction and CCRT phases, respectively. Conclusion: Weekly cetuximab with induction vinorelbine/cisplatin followed by concurrent cetuximab vinorelbine/cisplatin thoracic radiation is feasible with a manageable toxicity profile and clinically active. (C) 2015 Elsevier Ireland Ltd. All rights reserved.