title: Phase I study of gefitinib plus celecoxib in recurrent or metastatic squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  Effective and tolerable palliative treatments are needed for patients with incurable squamous cell carcinoma of the head and neck (SCCHN). Single-agent targeted therapies have limited activity in this setting. The feasibility of adding celecoxib to gefitinib for the treatment of incurable SCCHN is unknown.
  
  
  METHODS
  Nineteen patients with unresectable recurrent locoregional and/or distant metastatic SCCHN with progressive disease after at least one prior chemotherapy or chemoradiotherapy regimen were enrolled onto this single-institution phase I study. Three dose levels were explored: (1) celecoxib 200 mg twice daily plus gefitinib 250 mg daily; (2) celecoxib 400 mg twice daily plus gefitinib 250 mg daily; and (3) celecoxib 400 mg twice daily plus gefitinib 500 mg daily.
  
  
  RESULTS
  No dose-limiting toxicities were encountered at any dose level. The most common toxicities were acneiform rash, diarrhea, hand reaction, dyspepsia, and anemia. Four of 18 patients assessable for response (22%; 95% CI, 2% to 42%) achieved a confirmed partial response.
  
  
  CONCLUSIONS
  The combination of gefitinib 500 mg daily plus celecoxib 400 mg twice daily is well-tolerated. The encouraging responses seen in this early study suggest further evaluation of epidermal growth factor receptor and cyclooxygenase-2 inhibitors in SCCHN is warranted.
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. lwirth@partners.org
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Wirth
authors.forename: Robert I
authors.initials: RI
authors.lastname: Haddad
authors.forename: Neal I
authors.initials: NI
authors.lastname: Lindeman
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhao
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Lee
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Joshi
authors.forename: Charles M
authors.initials: CM
authors.lastname: Norris
authors.forename: Marshall R
authors.initials: MR
authors.lastname: Posner
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D000068579:Celecoxib; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010166:Palliative Care; D011720:Pyrazoles / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: D011720:Pyrazoles; D011799:Quinazolines; D013449:Sulfonamides; D000068579:Celecoxib; D000077156:Gefitinib