Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck.
BACKGROUND
We evaluated combined targeting with cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in squamous cell carcinoma of the head and neck (SCCHN).


METHODS
The combination was studied in human endothelial cells and head and neck and lung cancer xenograft model systems. Patients with recurrent or metastatic SCCHN were treated with weekly cetuximab and bevacizumab, 15 mg/kg on day 1 given intravenously every 21 days, until disease progression. Analysis of tumor biomarkers and related serum cytokines was performed.


RESULTS
Cetuximab plus bevacizumab enhanced growth inhibition both in vitro and in vivo, and resulted in potent reduction in tumor vascularization. In the clinical trial, 46 eligible patients were enrolled. The objective response rate was 16% and the disease control rate 73%. The median progression-free survival and overall survival were 2.8 and 7.5 months, respectively. Grade 3-4 adverse events were expected and occurred in less than 10% of patients. transforming growth factor alpha, placenta-derived growth factor, EGFR, VEGFR2 increased and VEGF decreased after treatment but did not correlate with treatment efficacy.


CONCLUSIONS
Cetuximab and bevacizumab are supported by preclinical observations and are well tolerated and active in previously treated patients with SCCHN.
Department of Medicine, Division of Hematology/Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. argiris@uthscsa.edu
A
A
Argiris
A P
AP
Kotsakis
T
T
Hoang
F P
FP
Worden
P
P
Savvides
M K
MK
Gibson
R
R
Gyanchandani
G R
GR
Blumenschein
H X
HX
Chen
J R
JR
Grandis
P M
PM
Harari
M S
MS
Kies
S
S
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D000068818:Cetuximab; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local
D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D000068818:Cetuximab