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Annals of Oncology Advance Access published online on October 22, 2009
Annals of Oncology, doi:10.1093/annonc/mdp390
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

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

C. H. Chung1,2,3,*, J. Aulino4, N. J. Muldowney3, H. Hatakeyama1, J. Baumann1, B. Burkey5, J. Netterville5, R. Sinard5, W. G. Yarbrough2,3,5, A. J. Cmelak6, R. J. Slebos2, Y. Shyr7, J. Parker8, J. Gilbert1 and B. A. Murphy1

1 Division of Hematology/Oncology, Department of Medicine
2 Department of Cancer Biology, Vanderbilt University School of Medicine
3 Vanderbilt-Ingram Comprehensive Cancer Center
4 Department of Radiology
5 Department of Otolaryngology
6 Department of Radiation Oncology
7 Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN
8 Expression Analysis, Inc., Durham, NC, USA

* Correspondence to: Dr C. H. Chung, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN 37232-6307, USA. Tel: +1-615-322-4967; Fax: +1-615-343-7602; E-mail: Christine.Chung{at}Vanderbilt.edu

Background: Our previous study has shown that nuclear factor-kappa B (NF-{kappa}B)-signaling pathway was associated with a higher rate of recurrence in head and neck squamous cell carcinoma (HNSCC). The combination of bortezomib, an NF-{kappa}B 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/m2 and docetaxel 40 mg/m2 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-{kappa}B-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-{kappa}B 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.

bortezomib, docetaxel, epidermal growth factor receptor, head and neck squamous cell carcinoma, nuclear factor-kappa B

Received for publication January 20, 2009. Revision received June 22, 2009. Accepted for publication June 26, 2009.


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