title: Prospective trial of synchronous bevacizumab, erlotinib, and concurrent chemoradiation in locally advanced head and neck cancer.
abstract: OBJECTIVE
  We assessed the safety and efficacy of synchronous VEGF and epidermal growth factor receptor (EGFR) blockade with concurrent chemoradiation (CRT) in locally advanced head and neck cancer (HNC).
  
  
  METHODS
  Newly diagnosed patients with stage III/IV HNC received a 2-week lead-in of bevacizumab and/or erlotinib, followed by both agents with concurrent cisplatin and twice daily radiotherapy. Safety was assessed using Common Toxicity Criteria version 3.0. The primary efficacy endpoint was clinical complete response (CR) rate after CRT.
  
  
  RESULTS
  Twenty-nine patients enrolled on study, with 27 completing therapy. Common grade III toxicities were mucositis (n = 14), dysphagia (n = 8), dehydration (n = 7), osteoradionecrosis (n = 3), and soft tissue necrosis (n = 2). Feeding tube placement was required in 79% but no patient remained dependent at 12-month posttreatment. Clinical CR after CRT was 96% [95% confidence interval (CI), 82%-100%]. Median follow-up was 46 months in survivors, with 3-year locoregional control and distant metastasis-free survival rates of 85% and 93%. Three-year estimated progression-free survival, disease-specific survival, and overall survival rates were 82%, 89%, and 86%, respectively. Dynamic contrast enhanced MRI (DCE-MRI) analysis showed that patients who had failed had lower baseline pretreatment median K(trans) values, with subsequent increases after lead-in therapy and 1 week of CRT. Patients who did not fail had higher median K(trans) values that decreased during therapy.
  
  
  CONCLUSIONS
  Dual VEGF/EGFR inhibition can be integrated with CRT in locally advanced HNC, with efficacy that compares favorably with historical controls albeit with an increased risk of osteoradionecrosis. Pretreatment and early DCE-MRI may prospectively identify patients at high risk of failure.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA. david.yoo@dm.duke.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Yoo
authors.forename: John P
authors.initials: JP
authors.lastname: Kirkpatrick
authors.forename: Oana
authors.initials: O
authors.lastname: Craciunescu
authors.forename: Gloria
authors.initials: G
authors.lastname: Broadwater
authors.forename: Bercedis L
authors.initials: BL
authors.lastname: Peterson
authors.forename: Madeline D
authors.initials: MD
authors.lastname: Carroll
authors.forename: Robert
authors.initials: R
authors.lastname: Clough
authors.forename: James R
authors.initials: JR
authors.lastname: MacFall
authors.forename: Jenny
authors.initials: J
authors.lastname: Hoang
authors.forename: Richard L
authors.initials: RL
authors.lastname: Scher
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Esclamado
authors.forename: Frank R
authors.initials: FR
authors.lastname: Dunphy
authors.forename: Neal E
authors.initials: NE
authors.lastname: Ready
authors.forename: David M
authors.initials: DM
authors.lastname: Brizel
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D000069347:Erlotinib Hydrochloride; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride