Pharmacogenetic predictors for EGFR-inhibitor-associated skin toxicity

S Parmar; C Schumann; S Rüdiger; S Boeck; V Heinemann; V Kächele; A Seeringer; T Paul; T Seufferlein; J C Stingl

doi:10.1038/tpj.2011.51

Pharmacogenetic predictors for EGFR-inhibitor-associated skin toxicity

Pharmacogenomics J. 2013 Apr;13(2):181-8. doi: 10.1038/tpj.2011.51. Epub 2011 Dec 13.

Authors

S Parmar¹, C Schumann, S Rüdiger, S Boeck, V Heinemann, V Kächele, A Seeringer, T Paul, T Seufferlein, J C Stingl

Affiliation

¹ Institute of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Helmholtzstrasse 20, Ulm, Germany.

PMID: 22158333
DOI: 10.1038/tpj.2011.51

Abstract

The aim of this study was to investigate pharmacogenetic determinants of skin rash associated with epidermal growth factor receptor (EGFR) inhibitor treatment. A total of 109 prospectively sampled cancer patients, receiving the first treatment with an EGFR inhibitor, were genotyped for functional EGFR polymorphisms and tagging variants in genes involved in receptor downstream signaling. Skin rash was absent in 26 (23.9%) patients and associated with shorter overall survival compared with patients presenting skin rash (P=0.005). The EGFR polymorphisms, 497G/A (P=0.008), and the haplotypes of the promoter variants, EGFR-216G/T and -191C/A (P=0.029), were associated with the appearance of skin rash. In addition, a common haplotype in the PIK3CA gene was associated with skin rash (P=0.045) and overall survival (P=0.009). In conclusion, genetic variation within the EGFR gene and its downstream signaling partner PIK3CA might predict EGFR-inhibitor-related skin rash.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal / administration & dosage
Antibodies, Monoclonal / adverse effects
Antibodies, Monoclonal, Humanized / administration & dosage
Antibodies, Monoclonal, Humanized / adverse effects
Cetuximab
Class I Phosphatidylinositol 3-Kinases
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / genetics*
Erlotinib Hydrochloride
Exanthema / chemically induced
Exanthema / genetics*
Exanthema / pathology
Female
Gefitinib
Genetic Association Studies
Haplotypes
Humans
Male
Middle Aged
Neoplasms / drug therapy
Neoplasms / genetics*
Neoplasms / pathology
Panitumumab
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism*
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / adverse effects*
Quinazolines / administration & dosage
Quinazolines / adverse effects

Substances

Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Protein Kinase Inhibitors
Quinazolines
Panitumumab
Erlotinib Hydrochloride
Phosphatidylinositol 3-Kinases
Class I Phosphatidylinositol 3-Kinases
PIK3CA protein, human
EGFR protein, human
ErbB Receptors
Cetuximab
Gefitinib