Efficacy of gemcitabine and cetuximab combination treatment in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) may be curable with surgery, radiation and chemotherapy in its early stages. However, recurrence and metastasis often prevail following primary treatment in advanced stage cases and are associated with significant morbidity and mortality. In this study we investigated the combination therapy of gemcitabine and cetuximab for HNSCC. The UM-SCC-6 and UM-SCC-23 HNSCC cell lines were analyzed following treatment with gemcitabine and cetuximab. To determine the mechanism of action of this combination treatment, the cell cycle distributions following gemcitabine and/or cetuximab treatment were analyzed by flow cytometry and apoptosis assay. Gemcitabine and cetuximab combination treatment exerted an enhanced cytotoxic effect. The cell cycle analysis demonstrated that cells accumulated in the S phase following gemcitabine treatment and G1 arrest occurred following cetuximab treatment. An increase in sub-G1 phase cells was also observed following treatment with the two drugs. In an apoptosis assay, caspase 3/7 activity was found to be higher when administering a combination of gemcitabine and cetuximab compared to each agent administered alone. Gemcitabine and cetuximab are individually effective against HNSCC and an enhanced growth inhibitory effect may be expected when these agents are used in combination.