title: A phase 2 study of bevacizumab with cisplatin plus intensity-modulated radiation therapy for stage III/IVB head and neck squamous cell cancer.
abstract: BACKGROUND
  For patients with stage III through IVB head and neck squamous cell carcinoma (HNSCC), concurrent high-dose cisplatin plus radiation therapy is a widely accepted standard of care. HNSCC tumors that express high levels of vascular endothelial growth factor have been associated with a worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation.
  
  
  METHODS
  Planned treatment consisted of definitive intensity-modulated radiation therapy (IMRT) (total, 70 grays) with concurrent cisplatin (50 mg/m(2) on days 1, 2, 22, 23, 43, and 44) and bevacizumab (15 mg/kg on days 1, 22, and 43). The primary endpoint was 2-year progression-free survival (PFS), and overall survival (OS) was a secondary endpoint.
  
  
  RESULTS
  Forty-two previously untreated patients (34 men and 8 women; median age, 55 years; range, 27-75 years) with stage III through IV HNSCC without distant metastasis (oropharyngeal carcinoma, 39 patients; laryngeal carcinoma, 3 patients) were treated. Human papillomavirus (HPV) status by was determined by in situ hybridization (HPV positive, 16 patients; HPV negative, 14 patients, unknown HPV status, 12 patients). The toxicities (determined according to version 3.0 of Common Terminology Criteria for Adverse Events Common) that were experienced by all patients (any grade) were mucositis, lymphopenia, leukopenia, throat pain, fatigue, and anemia. There were 2 treatment-related deaths, including 1 sudden death and 1 death from aspiration pneumonia. The median follow-up was approximately 31.8 months (range, <3 to 51 months). The 2-year PFS rate was 75.9% (95% confidence interval, 63.9%-90.1%), and the 2-year OS rate was 88% (95% confidence interval, 78.6%-98.4%). Among 32 patients for whom post-treatment Head and Neck Performance Status Scores were obtained (median, 5.6 months after completing radiation therapy), scores of 100 for eating, speech, and diet, respectively, were recorded among 75%, 84%, and 50% of patients.
  
  
  BACKGROUND
  The addition of bevacizumab to high-dose cisplatin plus IMRT did not appear to increase toxicity to unacceptable levels among patients with HNSCC, and the efficacy results were encouraging.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. furym@mskcc.org
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Fury
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Lee
authors.forename: Eric
authors.initials: E
authors.lastname: Sherman
authors.forename: Donna
authors.initials: D
authors.lastname: Lisa
authors.forename: Katherine
authors.initials: K
authors.lastname: Kelly
authors.forename: Brynna
authors.initials: B
authors.lastname: Lipson
authors.forename: Diane
authors.initials: D
authors.lastname: Carlson
authors.forename: Hilda
authors.initials: H
authors.lastname: Stambuk
authors.forename: Sofia
authors.initials: S
authors.lastname: Haque
authors.forename: Ronglai
authors.initials: R
authors.lastname: Shen
authors.forename: Dennis
authors.initials: D
authors.lastname: Kraus
authors.forename: Jatin
authors.initials: J
authors.lastname: Shah
authors.forename: David G
authors.initials: DG
authors.lastname: Pfister
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D050397:Radiotherapy, Intensity-Modulated
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002945:Cisplatin