title: Phase 2 trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and hyperfractionated intensity-modulated radiation therapy for locally advanced head and neck cancer.
abstract: BACKGROUND
  The objective of this phase 2 study was to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated-boost (SIB), intensity-modulated radiation therapy (IMRT) into a well described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen.
  
  
  METHODS
  Patients with stage IVA and IVB or high-risk stage III squamous cell carcinomas of the head and neck were enrolled on a phase 2 trial. Prior organ-conserving surgery or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low-risk volumes (43.2 gray [Gy] to 48 Gy) and intermediate-risk volumes (54-63 Gy). A separate IMRT cone-down plan was targeted to macroscopic disease (72 Gy). The median radiation dose was 72 Gy (range, 60-72 Gy) administered in 1.5 Gy fractions twice daily during Weeks 1, 3, 5, 7 and 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m²), HU (500 mg twice daily), and cetuximab (250 mg/m²).
  
  
  RESULTS
  From January 2007 through April 2008, 33 patients were enrolled. At a median follow-up of 24 months, the 2-year rates of locoregional control, distant control, disease-free survival, and overall survival were 83%, 79%, 69%, and 86%, respectively. Grade 3 toxicity consisted of mucositis in 33% of patients, radiation dermatitis in 15%of patients, anemia in 18% of patients, leukopenia in 18% of patients, neutropenia in 12% of patients, and thrombocytopenia in 3% of patients. Most patients (64%) were able to tolerate treatment without a feeding tube, and there were no acute or late grade ≥4 adverse events.
  
  
  CONCLUSIONS
  The current results indicated that concurrent 5-FU, HU, and cetuximab plus SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy into curative therapy for patients with locally advanced head and neck cancer.
authors.affiliation: Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York, USA. johnnykaomd@gmail.com
authors.forename: Johnny
authors.initials: J
authors.lastname: Kao
authors.forename: Eric M
authors.initials: EM
authors.lastname: Genden
authors.forename: Vishal
authors.initials: V
authors.lastname: Gupta
authors.forename: Edelweiss L
authors.initials: EL
authors.lastname: Policarpio
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Burri
authors.forename: Michael
authors.initials: M
authors.lastname: Rivera
authors.forename: Vivek
authors.initials: V
authors.lastname: Gurudutt
authors.forename: Peter M
authors.initials: PM
authors.lastname: Som
authors.forename: Marita
authors.initials: M
authors.lastname: Teng
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Packer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D000068818:Cetuximab; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D050397:Radiotherapy, Intensity-Modulated
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D005472:Fluorouracil; D006918:Hydroxyurea