Abstract | PURPOSE: 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 >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.
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Authors | Konrad Klinghammer, Maren Knödler, Alexander Schmittel, Volker Budach, Ulrich Keilholz, Ingeborg Tinhofer |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 16
Issue 1
Pg. 304-10
(Jan 01 2010)
ISSN: 1557-3265 [Electronic] United States |
PMID | 20028750
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Taxoids
- Docetaxel
- Cetuximab
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Topics |
- 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
- Docetaxel
- 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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