title: Phase I trial of gefitinib in combination with radiation or chemoradiation for patients with locally advanced squamous cell head and neck cancer.
abstract: OBJECTIVE
  To establish the safety and toxicity profile of daily gefitinib with radiation alone or with concurrent chemoradiotherapy in previously untreated patients with locally advanced squamous cell head and neck cancer (LAHNC).
  
  
  METHODS
  Patients with intermediate-stage LAHNC were treated with concomitant boost radiation (RT) alone with escalating doses of daily gefitinib (250 or 500 mg; cohort I). Once a safety profile was determined with RT alone, patients with high-risk disease were then treated with daily gefitinib (250 or 500 mg), weekly cisplatin (CDDP; 30 mg/m2), and once-daily RT (cohort II). Patients also received post-RT gefitinib at 250 mg daily for a period of up to 2 years.
  
  
  RESULTS
  Twenty-three patients were enrolled and assessable for toxicity. No dose-limiting toxicities (DLTs) were observed in patients treated in cohort I at either 250 or 500 mg of gefitinib daily with concomitant boost RT to 72 Gy. In patients receiving chemoradiotherapy and gefitinib (cohort II), DLTs included one grade 4 diarrhea and one grade 4 neutropenic fever. Fifteen patients started maintenance gefitinib, and eight (53%) experienced grade 1 to 2 acne-like skin rash and diarrhea, but no grade 3 or 4 toxicity occurred.
  
  
  CONCLUSIONS
  Gefitinib (250 or 500 mg daily) was well tolerated with concomitant boost RT or concurrent chemoradiotherapy with weekly CDDP. Protracted administration of gefitinib for up to 2 years at 250 mg daily was also tolerated well.
authors.affiliation: Department of Radiation Oncology, University of Colorado, Aurora, CO, USA.
authors.forename: Changhu
authors.initials: C
authors.lastname: Chen
authors.forename: Madeleine
authors.initials: M
authors.lastname: Kane
authors.forename: John
authors.initials: J
authors.lastname: Song
authors.forename: John
authors.initials: J
authors.lastname: Campana
authors.forename: Adam
authors.initials: A
authors.lastname: Raben
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hu
authors.forename: Louis
authors.initials: L
authors.lastname: Harrison
authors.forename: Harry
authors.initials: H
authors.lastname: Quon
authors.forename: Janet
authors.initials: J
authors.lastname: Dancey
authors.forename: Anna
authors.initials: A
authors.lastname: Baron
authors.forename: Sherif
authors.initials: S
authors.lastname: Said
authors.forename: S Gail
authors.initials: SG
authors.lastname: Eckhardt
authors.forename: David
authors.initials: D
authors.lastname: Raben
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D002945:Cisplatin; D000077156:Gefitinib