In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 16, No. 1 ( 2010-01-01), p. 304-310
Abstract:
Purpose: 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. Experimental Design: 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. Results: Overall, 21 patients (41%) developed skin rash with grade & gt;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. Conclusions: Our study revealed an influence of the EGFR-R521K genotype on skin toxicity and suggested its relation to clinical activity of cetuximab/docetaxel treatment. Clin Cancer Res; 16(1); 304–10
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-09-1928
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
