Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/76395
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Dual targeting of the epidermal growth factor receptor using the combination of cetuximab and erlotinib: Preclinical evaluation and results of the Phase II DUX Study in chemotherapy-refractory, advanced colorectal cancer
Author: Weickhardt, A.
Price, T.
Chong, G.
Gebski, V.
Pavlakis, N.
Johns, T.
Azad, A.
Skrinos, E.
Fluck, K.
Dobrovic, A.
Salemi, R.
Scott, A.
Mariadason, J.
Tebbutt, N.
Citation: Journal of Clinical Oncology, 2012; 30(13):1505-1512
Publisher: Amer Soc Clinical Oncology
Issue Date: 2012
ISSN: 0732-183X
0732-183X
Statement of
Responsibility: 
Andrew J. Weickhardt, Tim J. Price, Geoff Chong, Val Gebski, Nick Pavlakis, Terrance G. Johns, Arun Azad, Effie Skrinos, Kate Fluck, Alexander Dobrovic, Renato Salemi, Andrew M. Scott, John M. Mariadason, and Niall C. Tebbutt
Abstract: <h4>Purpose</h4>This preclinical and phase II study evaluated the efficacy and safety of the combination of cetuximab and erlotinib in metastatic colorectal cancer (mCRC).<h4>Patients and methods</h4>The activity and mechanism of action of the combination of cetuximab plus erlotinib were investigated in vitro in colorectal cancer cell lines. In the clinical study, patients with chemotherapy-refractory mCRC were treated with cetuximab 400 mg/m(2) as a loading dose and then weekly cetuximab 250 mg/m(2) with erlotinib 100 mg orally daily. The primary end point was response rate (RR), which was evaluated separately in KRAS wild-type (WT) versus KRAS mutant tumors. Secondary end points included toxicity, progression-free survival (PFS), and overall survival. Target accrual was 50 patients, with a one-stage design.<h4>Results</h4>Preclinical studies demonstrated synergistic activity of cetuximab and erlotinib cotreatment on growth inhibition of colon cancer cell lines both as a result of enhanced inhibition of the epidermal growth factor receptor pathway and differential effects on STAT3. In the clinical study, 50 patients were enrolled, with 48 patients evaluable for response. The overall RR was 31% (95% CI, 26% to 57%), with a median PFS of 4.6 months (95% CI, 2.8 to 5.6 months). RR was 41% (95% CI, 26% to 57%) in KRAS WT tumors, with a median PFS of 5.6 months (95% CI, 2.9 to 5.6 months). There was no response in 11 patients with KRAS mutations. Frequent grade 3 and 4 toxicities were rash (48%), hypomagnesaemia (18%), and fatigue (10%).<h4>Conclusion</h4>The combination of cetuximab and erlotinib synergistically inhibits growth of colon cancer cell lines, achieves promising efficacy in patients with KRAS WT mCRC, and merits evaluation in further randomized studies.
Keywords: Cell Line, Tumor
Humans
Colorectal Neoplasms
Quinazolines
ras Proteins
Proto-Oncogene Proteins
Antineoplastic Combined Chemotherapy Protocols
Antibodies, Monoclonal
Protein Kinase Inhibitors
Disease-Free Survival
Treatment Outcome
Analysis of Variance
Transfection
Signal Transduction
Cell Proliferation
Drug Synergism
Drug Resistance, Neoplasm
Mutation
Time Factors
Adult
Aged
Aged, 80 and over
Middle Aged
Australia
Female
Male
Proto-Oncogene Proteins p21(ras)
STAT3 Transcription Factor
Kaplan-Meier Estimate
Molecular Targeted Therapy
Antibodies, Monoclonal, Humanized
ErbB Receptors
Cetuximab
Erlotinib Hydrochloride
Rights: © 2012 by American Society of Clinical Oncology
DOI: 10.1200/JCO.2011.38.6599
Grant ID: ARC
Published version: http://dx.doi.org/10.1200/jco.2011.38.6599
Appears in Collections:Aurora harvest
Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.