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

Howard S. Moskowitz, William E. Gooding, Sufi M. Thomas, Maria L. Freilino, Neil Gross, Athanassios Argiris, Jennifer R. Grandis, Robert L. Ferris

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1136-1145
Number of pages10
JournalOral Oncology
Volume48
Issue number11
DOIs
StatePublished - Nov 2012
Externally publishedYes

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Prostaglandin-Endoperoxide Synthases
Head and Neck Neoplasms
Epidermal Growth Factor
Sulindac
Biomarkers
Enzyme-Linked Immunosorbent Assay
Serum
Neoadjuvant Therapy
Placebos
Epidermal Growth Factor Receptor
G-Protein-Coupled Receptors
Protein-Tyrosine Kinases
Blood Proteins
Interleukin-6
Erlotinib Hydrochloride
Clinical Trials
Therapeutics
Neoplasms

Keywords

  • Biomarkers
  • COX
  • EGFR
  • Erlotinib
  • HNSCC
  • Sulindac

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

Cite this

Serum biomarker modulation following molecular targeting of epidermal growth factor and cyclooxygenase pathways : A pilot randomized trial in head and neck cancer. / Moskowitz, Howard S.; Gooding, William E.; Thomas, Sufi M.; Freilino, Maria L.; Gross, Neil; Argiris, Athanassios; Grandis, Jennifer R.; Ferris, Robert L.

In: Oral Oncology, Vol. 48, No. 11, 11.2012, p. 1136-1145.

Research output: Contribution to journalArticle

Moskowitz, Howard S. ; Gooding, William E. ; Thomas, Sufi M. ; Freilino, Maria L. ; Gross, Neil ; Argiris, Athanassios ; Grandis, Jennifer R. ; Ferris, Robert L. / Serum biomarker modulation following molecular targeting of epidermal growth factor and cyclooxygenase pathways : A pilot randomized trial in head and neck cancer. In: Oral Oncology. 2012 ; Vol. 48, No. 11. pp. 1136-1145.
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T2 - A pilot randomized trial in head and neck cancer

AU - Moskowitz, Howard S.

AU - Gooding, William E.

AU - Thomas, Sufi M.

AU - Freilino, Maria L.

AU - Gross, Neil

AU - Argiris, Athanassios

AU - Grandis, Jennifer R.

AU - Ferris, Robert L.

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N2 - 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.

AB - 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.

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