title: Phase 2 study of concurrent cetuximab plus definitive thoracic radiation therapy followed by consolidation docetaxel plus cetuximab in poor prognosis or elderly patients with locally advanced non-small cell lung cancer.
abstract: BACKGROUND
  Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab.
  
  
  METHODS
  Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-"dry" IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR).
  
  
  RESULTS
  From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board-approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications.
  
  
  CONCLUSIONS
  Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Dilling
authors.affiliation: Department of Senior Adult Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Martine
authors.initials: M
authors.lastname: Extermann
authors.affiliation: Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Jongphil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Supportive Care Medicine, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Lora M
authors.initials: LM
authors.lastname: Thompson
authors.affiliation: Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Binglin
authors.initials: B
authors.lastname: Yue
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Stevens
authors.affiliation: Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Scott
authors.initials: S
authors.lastname: Antonia
authors.affiliation: Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Jhanelle
authors.initials: J
authors.lastname: Gray
authors.affiliation: Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Charles
authors.initials: C
authors.lastname: Williams
authors.affiliation: Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Eric
authors.initials: E
authors.lastname: Haura
authors.affiliation: Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Mary
authors.initials: M
authors.lastname: Pinder-Schenck
authors.affiliation: Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Tawee
authors.initials: T
authors.lastname: Tanvetyanon
authors.affiliation: Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Sungjune
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida. Electronic address: alberto.chiappori@moffitt.org.
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiappori
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000068818:Cetuximab; D002985:Clinical Protocols; D060830:Consolidation Chemotherapy / Q000379:methods; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009068:Movement; D011014:Pneumonia / Q000139:chemically induced; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D012119:Respiration; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D000068818:Cetuximab