Serum biomarker modulation following molecular targeting of epidermal growth factor and cyclooxygenase pathways: A pilot randomized trial in head and neck cancer

Autor: Athanassios Argiris, William E. Gooding, Maria L. Freilino, Sufi M. Thomas, Jennifer R. Grandis, Neil D. Gross, Howard S. Moskowitz, Robert L. Ferris
Rok vydání: 2012
Předmět:
Male
Oncology
Cancer Research
Pilot Projects
HNSCC
Tyrosine-kinase inhibitor
Placebos
Sulindac
Epidermal growth factor
Multiplex
Prospective Studies
Epidermal growth factor receptor
Erlotinib Hydrochloride
Cancer
EGFR inhibitors
screening and diagnosis
Tumor
biology
Hepatocyte Growth Factor
Middle Aged
Neoadjuvant Therapy
ErbB Receptors
Detection
Erlotinib
Head and Neck Neoplasms
6.1 Pharmaceuticals
Carcinoma
Squamous Cell
Public Health and Health Services
Female
Oral Surgery
4.2 Evaluation of markers and technologies
medicine.drug
Adult
medicine.medical_specialty
medicine.drug_class
EGFR
Clinical Trials and Supportive Activities
Oncology and Carcinogenesis
Antineoplastic Agents
Enzyme-Linked Immunosorbent Assay
Article
Double-Blind Method
Clinical Research
Internal medicine
Biomarkers
Tumor
medicine
Humans
Oncology & Carcinogenesis
Protein Kinase Inhibitors
Aged
Interleukin-6
business.industry
Prevention
Carcinoma
COX
Evaluation of treatments and therapeutic interventions
Transforming Growth Factor alpha
Squamous Cell
Dentistry
Quinazolines
Cancer research
biology.protein
business
Biomarkers
Zdroj: Oral oncology, vol 48, iss 11
ISSN: 1368-8375
Popis: Summary Objective Targeting the epidermal growth factor receptor (EGFR) using the tyrosine kinase inhibitor (TKI) erlotinib has demonstrated activity in aerodigestive tract malignancies. Co-targeting of the G-protein-coupled receptor cyclooxygenase (COX) with EGFR inhibitors has shown promise in preclinical models and early phase clinical studies. Materials and Methods We studied the modulation of serum proteins after neoadjuvant treatment with erlotinib with or without sulindac in head and neck cancer patients. In a prospective, randomized, double-blind clinical trial, paired serum samples were obtained before and after neoadjuvant treatment in three groups of patients ( n = 23 total), who were randomized to receive 7–14 consecutive days of erlotinib alone, erlotinib plus sulindac, or placebo. Two separate multiplexed ELISA systems (SearchLight™ or Luminex™) were used to measure serum biomarkers. HGF and IL-6 levels were tested on both systems, and validated using single analyte ELISAs. Results Several analytes were significantly altered (generally decreased) post-treatment, in patients who received erlotinib (with or without sulindac) as well as in the placebo groups. No single analyte was differentially altered across the three treatment groups using either multiplex platform. Single HGF ELISA suggested a nonspecific decrease in all patients. Conclusion These results demonstrate the importance of a placebo group when assessing changes in expression of serum biomarkers. While multiplex platforms can provide quantitative information on a large number of serum analytes, results should be cautiously compared across platforms due to their intrinsic features. Furthermore, the dynamic range of expression of a single analyte is constrained in multiplex versus standard ELISA.
Databáze: OpenAIRE
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