title: A multicenter phase II study of cetuximab in combination with chest radiotherapy and consolidation chemotherapy in patients with stage III non-small cell lung cancer.
abstract: BACKGROUND
  Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5 Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63 Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH).
  
  
  RESULTS
  Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes.
  
  
  CONCLUSIONS
  The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.
authors.affiliation: Department of Hematology/Oncology, Winship Cancer Institute of Emory University School of Medicine, Atlanta, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Ramalingam
authors.affiliation: Department of Medical Oncology, University Hospital of Heraklion, Crete, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Kotsakis
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Tarhini
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Heron
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA.
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA.
authors.forename: D
authors.initials: D
authors.lastname: Friedland
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Petro
authors.affiliation: Department of Medical Oncology, Memorial Cancer Institute, Pembroke Pines, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Raez
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Brahmer
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Greenberger
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dacic
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Pittsburgh, USA.
authors.forename: P
authors.initials: P
authors.lastname: Hershberger
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Landreneau
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Luketich
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Belani
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, USA. Electronic address: argiris@uthscsa.edu.
authors.forename: A
authors.initials: A
authors.lastname: Argiris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D000068818:Cetuximab; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011878:Radiotherapy / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab
keywords: Cetuximab; Chemotherapy; EGFR; Non-small cell lung cancer; Radiotherapy