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 - PubMed (original) (raw)

Clinical Trial

. 2010 Apr;21(4):864-870.

doi: 10.1093/annonc/mdp390. Epub 2009 Oct 22.

J Aulino 2, N J Muldowney 3, H Hatakeyama 4, J Baumann 4, B Burkey 5, J Netterville 5, R Sinard 5, W G Yarbrough 6, A J Cmelak 7, R J Slebos 8, Y Shyr 9, J Parker 10, J Gilbert 4, B A Murphy 4

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Clinical Trial

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 Chung et al. Ann Oncol. 2010 Apr.

Abstract

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.

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Figures

Figure 1.

Figure 1.

Kaplan–Meier plots comparing patients with partial response (PR) and stable diseases (SD) versus progressive disease (PD). (A) Overall survival; median survival time 9.4 versus 4.3 months; log-rank test P = 0.028. (B) Progression-free survival; median survival time 3.0 versus 1.5 months; log-rank test P <0.0001. Red line: PR/SD; black line: PD.

Figure 2.

Figure 2.

Hierarchical clustering of 25 samples using the 111-gene nuclear factor-kappa B (NF-κB) signature known to be modulated by NF-κB as previously published [10, 26]. Red: PR, partial response and SD, stable disease; blue: PD, progressive disease; green: normal mucosa adjacent to the tumors; purple squares: higher gene expression; yellow squares: lower gene expression.

Figure 3.

Figure 3.

Hierarchical clustering of 25 samples using the 239 genes that were differentially expressed between tumors with partial response (PR)/stable disease (SD) and progressive disease (PD). Red: PR/SD; blue: PD; green: normal mucosa adjacent to the tumors; purple squares: higher gene expression; yellow squares: lower gene expression.

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