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 |
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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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