title: A randomized phase II study of 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy compared with bevacizumab plus 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy for intermediate-stage and T4N0-1 head and neck cancers.
abstract: BACKGROUND
  We conducted a randomized phase II study to evaluate the impact of adding bevacizumab (B) to 5-fluorouracil (5-FU), hydroxyurea (HU), and radiotherapy (FHX) for intermediate-stage and select T4 head and neck squamous cell cancers (HNSCC).
  
  
  METHODS
  Eligible patients had newly diagnosed HNSCC. Randomization was 2:1 in favor of BFHX. All patients received 500 mg HU p.o. b.i.d., 600 mg/m(2)/day continuous infusion 5-FU, and b.i.d. radiotherapy with or without bevacizumab 10 mg/kg administered on day 1 of each 14-day cycle. Patients received five cycles consisting of chemoradiotherapy for 5 days followed by 9 days without therapy.
  
  
  RESULTS
  Twenty-six patients were enrolled (19 BFHX and 7 FHX). The study was halted following unexpected locoregional progression. Two-year survival was 68%; 89% treated with FHX and 58% (95% confidence interval 33% to 78%) treated with BFHX. Two-year locoregional control was 80% after chemoradiotherapy and 85% after surgical salvage. All locoregional progression occurred in T4 tumors randomized to BFHX. Two patients receiving BFHX died during therapy, and one died shortly after therapy. No catastrophic bleeding events were seen.
  
  
  CONCLUSIONS
  Locoregional progression seen in T4N0-1 tumors treated with BFHX was unexpected and led to study termination. The addition of bevacuzimab to chemoradiotherapy for HNSCC should be limited clinical trials.
authors.affiliation: Department of Radiation Oncology, Duke University, Durham 27710, USA. joseph.salama@duke.edu
authors.forename: J K
authors.initials: JK
authors.lastname: Salama
authors.forename: D J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: K M
authors.initials: KM
authors.lastname: Stenson
authors.forename: E A
authors.initials: EA
authors.lastname: Blair
authors.forename: M E
authors.initials: ME
authors.lastname: Witt
authors.forename: R
authors.initials: R
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Kunnavakkam
authors.forename: E E W
authors.initials: EE
authors.lastname: Cohen
authors.forename: T
authors.initials: T
authors.lastname: Seiwert
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005472:Fluorouracil; D006918:Hydroxyurea