Phase I study of gefitinib plus celecoxib in recurrent or metastatic squamous cell carcinoma of the head and neck

J Clin Oncol. 2005 Oct 1;23(28):6976-81. doi: 10.1200/JCO.2005.02.4182. Epub 2005 Sep 19.

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Celecoxib
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Gefitinib
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Palliative Care
  • Pyrazoles / administration & dosage
  • Quinazolines / administration & dosage
  • Sulfonamides / administration & dosage

Substances

  • Pyrazoles
  • Quinazolines
  • Sulfonamides
  • Celecoxib
  • Gefitinib