WEDNESDAY, Feb. 20 (HealthDay News) -- The combination of the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) erlotinib with the cyclooxygenase-2 inhibitor celecoxib shows promise as a chemoprevention regimen for patients at high risk of developing head and neck cancer, according to research published online Feb. 19 in Clinical Cancer Research.

Dong M. Shin, M.D., of Emory University in Atlanta, and colleagues evaluated the potential of using erlotinib plus celecoxib in the prevention of head and neck cancer in both the preclinical and clinical settings.

The researchers found that, compared with either agent alone, the combined use of erlotinib and celecoxib in preclinical studies significantly inhibited head and neck cancer cell growth more effectively. In a phase I chemoprevention study, the overall pathologic response rate was 71 percent. Samples from patients treated with the combination exhibited downregulation of EGFR, phosphorylated extracellular signal regulated kinase, and phosphorylated ribosomal protein S6 levels.

"The changes in some protein markers were significantly correlated with the clinical outcome of patients on a phase I chemoprevention trial, although the sample size is small. Our preclinical studies not only confirm the clinical findings but also provide insight into the mechanisms of action of combined treatment with erlotinib and celecoxib in head and neck cancer prevention," the authors write. "Together, our investigation combining both preclinical studies and the biomarker-driven phase I clinical trial serves as a proof-of-principle to justify future chemoprevention trials that target multiple signal transduction pathways involved in carcinogenesis of head and neck cancer."

Abstract
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