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.
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.


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.


CONCLUSIONS
Further understanding of treatment resistance and interactions between bortezomib and docetaxel may provide novel approaches in managing HNSCC.
Division of Hematology/Oncology, Department of Medicine; Department of Cancer Biology, Vanderbilt University School of Medicine; Vanderbilt-Ingram Comprehensive Cancer Center. Electronic address: Christine.Chung@Vanderbilt.edu.
C H
CH
Chung
Department of Radiology.
J
J
Aulino
Vanderbilt-Ingram Comprehensive Cancer Center.
N J
NJ
Muldowney
Division of Hematology/Oncology, Department of Medicine.
H
H
Hatakeyama
Division of Hematology/Oncology, Department of Medicine.
J
J
Baumann
Department of Otolaryngology.
B
B
Burkey
Department of Otolaryngology.
J
J
Netterville
Department of Otolaryngology.
R
R
Sinard
Department of Cancer Biology, Vanderbilt University School of Medicine; Vanderbilt-Ingram Comprehensive Cancer Center; Department of Otolaryngology.
W G
WG
Yarbrough
Department of Radiation Oncology.
A J
AJ
Cmelak
Department of Cancer Biology, Vanderbilt University School of Medicine.
R J
RJ
Slebos
Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN.
Y
Y
Shyr
Expression Analysis, Inc., Durham, NC, USA.
J
J
Parker
Division of Hematology/Oncology, Department of Medicine.
J
J
Gilbert
Division of Hematology/Oncology, Department of Medicine.
B A
BA
Murphy
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000077143:Docetaxel; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D009362:Neoplasm Metastasis; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D054316:Biomarkers, Pharmacological; D001897:Boronic Acids; D016328:NF-kappa B; D011719:Pyrazines; D043823:Taxoids; D000077143:Docetaxel; D000069286:Bortezomib