Association of epidermal growth factor receptor polymorphism, skin toxicity, and outcome in patients with squamous cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment.

Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR), has shown clinical efficacy in squamous cell carcinoma of the head and neck with prolonged progression-free (PFS) and overall survival (OS). In this study, we analyzed whether cetuximab-induced skin rash was correlated with distinct polymorphisms within the EGFR gene known to modulate EGFR expression, ligand binding, or signaling activity.
Fifty-one patients enrolled in a single-arm phase II multicenter study for second-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck with cetuximab/docetaxel were genotyped for two genetic variations in the EGFR gene, a point substitution G-->A in exon 13 resulting in an amino acid substitution in position 521 (EGFR-R521K) and a CA repeat (CA-SSR) polymorphism in intron 1. Association between genotypes and incidence/grade of skin rash was determined by Fisher's exact test. The predictive value of genotypes for PFS and OS was determined using the log-rank test.
Overall, 21 patients (41%) developed skin rash with grade >1 within 6 weeks of treatment. The common EGFR-R521K genotype (G/G) was significantly associated with increased skin toxicity (P = 0.024) and showed a trend toward reduced risk of tumor progression (hazard ratio, 0.55; 95% confidence interval, 0.27-1.08; P = 0.08), whereas no correlation of the EGFR-R521K genotype with OS could be observed (P = 0.20). No significant interaction between CA-SSR polymorphism and skin toxicity, PFS, or OS could be detected.
Our study revealed an influence of the EGFR-R521K genotype on skin toxicity and suggested its relation to clinical activity of cetuximab/docetaxel treatment.
AuthorsKonrad Klinghammer, Maren Knödler, Alexander Schmittel, Volker Budach, Ulrich Keilholz, Ingeborg Tinhofer
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 16 Issue 1 Pg. 304-10 (Jan 1 2010) ISSN: 1078-0432 [Print] United States
PMID20028750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Taxoids
  • docetaxel
  • Cetuximab
  • Antibodies, Monoclonal (administration & dosage, adverse effects)
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
  • Carcinoma, Squamous Cell (drug therapy, genetics)
  • Cetuximab
  • Disease-Free Survival
  • Exanthema (chemically induced, genetics)
  • Female
  • Genes, erbB-1
  • Head and Neck Neoplasms (drug therapy, genetics)
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Survival Analysis
  • Taxoids (administration & dosage, adverse effects)
  • Treatment Outcome

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