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

Lung Cancer. 2015 Sep;89(3):249-54. doi: 10.1016/j.lungcan.2015.06.004. Epub 2015 Jun 17.

Abstract

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/m2, day 1, week 1; maintenance dose 250 mg/m2 from week 2 to the end of CCRT) and induction vinorelbine (25 mg/m2, days 1 and 8) and cisplatin (75 mg/m2, 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/m2, days 1 and 8; cisplatin 25mg/m2, 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.

Keywords: Cetuximab; Concurrent chemoradiotherapy; Induction chemotherapy; Locally advanced; Non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Cetuximab / administration & dosage
  • Chemoradiotherapy* / adverse effects
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Female
  • Humans
  • Induction Chemotherapy
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Risk Factors
  • Survival Analysis
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine

Substances

  • Vinblastine
  • Cetuximab
  • Cisplatin
  • Vinorelbine