James Netterville
Faculty Member

Nuclear factor-kappa B pathway and response in a phase II trial of bortezomib and docetaxel in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

Chung CH, Aulino J, Muldowney NJ, Hatakeyama H, Baumann J, Burkey B, Netterville J, Sinard R, Yarbrough WG, Cmelak AJ, Slebos RJ, Shyr Y, Parker J, Gilbert J, Murphy BA
Ann Oncol. 2010 21 (4): 864-870

PMID: 19850643 · PMCID: PMC2844946 · DOI:10.1093/annonc/mdp390

BACKGROUND - Our previous study has shown that nuclear factor-kappa B (NF-kappaB)-signaling pathway was associated with a higher rate of recurrence in head and neck squamous cell carcinoma (HNSCC). The combination of bortezomib, an NF-kappaB inhibitor by inhibition of proteasomes, plus docetaxel was assessed for efficacy and toxicity.

MATERIALS AND METHODS - Patients with recurrent and/or metastatic HNSCC were enrolled on a phase II bortezomib/docetaxel trial (bortezomib 1.6 mg/m(2) and docetaxel 40 mg/m(2) on days 1 and 8 of a 21-day cycle). Response was assessed using RECIST. Tissue specimens were evaluated for the presence of human papillomavirus (HPV) and expression of NF-kappaB-associated genes.

RESULTS - Twenty-one of 25 enrolled patients were assessable for response; one partial response (PR, 5%), 10 stable disease (SD, 48%) and 10 progressive disease (PD, 48%). Patients with PR/SD had significantly longer survival compared with patients with PD and the regimen was well tolerated. Only one of 20 tumors was positive for HPV. Patients with PD had higher expression of NF-kappaB and epidermal growth factor receptor-associated genes in their tumors by gene expression analysis.

CONCLUSION - Further understanding of treatment resistance and interactions between bortezomib and docetaxel may provide novel approaches in managing HNSCC.

MeSH Terms (20)

Antineoplastic Combined Chemotherapy Protocols Biomarkers, Pharmacological Boronic Acids Bortezomib Carcinoma, Squamous Cell Docetaxel Female Gene Expression Regulation, Neoplastic Head and Neck Neoplasms Humans Male Middle Aged Neoplasm Metastasis NF-kappa B Pyrazines Recurrence Signal Transduction Survival Analysis Taxoids Treatment Outcome

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