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


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.


CONCLUSIONS
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.
Department of Otolaryngology, Johns Hopkins Hospital, Baltimore, MD, USA.
Howard S
HS
Moskowitz
William E
WE
Gooding
Sufi M
SM
Thomas
Maria L
ML
Freilino
Neil
N
Gross
Athanassios
A
Argiris
Jennifer R
JR
Grandis
Robert L
RL
Ferris
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D066246:ErbB Receptors / Q000097:blood; D000069347:Erlotinib Hydrochloride; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000188:drug therapy; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D010865:Pilot Projects; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D013467:Sulindac / Q000008:administration & dosage; D016211:Transforming Growth Factor alpha / Q000097:blood
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015850:Interleukin-6; D010919:Placebos; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D016211:Transforming Growth Factor alpha; D013467:Sulindac; D017228:Hepatocyte Growth Factor; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors