HLA polymorphisms influence the development of skin rash arising from treatment with EGF receptor inhibitors.

Abstract

AIM:

Development of a skin rash under treatment with EGF receptor (EGFR) inhibitors (EGFRIs) has been linked to a favorable prognosis in some studies, suggesting a possible immunological role for EGFRIs in addition to direct antagonistic downstream effects. The present study aimed to investigate whether particular HLA polymorphisms found in cancer patients treated with EGFRIs are associated with the development of skin rash and overall survival rates.

PATIENTS & METHODS:

HLA typing was performed on 105 cancer patients and the development of skin rash was rated during the first 4 weeks of therapy with EGFRIs.

RESULTS:

A significantly lower incidence of skin rash was found in patients carrying the HLA-A*02:01 or HLA-A*03:01 alleles (hazard ratio: 0.277; 95% CI: 0.121-0.634; p = 0.002 and hazard ratio: 0.292; 95% CI: 0.113-0.752; p = 0.011, respectively); however, no association with worse survival was seen.

CONCLUSION:

The chances of developing a skin rash in patients treated with EGFRIs may be lower in patients that carry the HLA-A*02:01 or HLA-A*03:01 alleles, while the antitumor efficacy of EGFRIs does not seem to be significantly impaired in these patients.

• Authors: Daniel Fuerst, Sumit Parmar, Christian Schumann, Stefan Rüdiger, Stefan Boeck, Volker Heinemann, Volker Kaechele, Kristina Stiebel, Tanusree Paul, Thomas Seufferlein, Joannis Mytilineos, Julia Carolin Stingl
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 13 Issue 13 Pg. 1469-76 (Oct 2012) ISSN: 1744-8042 [Electronic] England
• PMID: 23057547 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• HLA Antigens
• HLA-A Antigens
• HLA-B Antigens
• HLA-C Antigens
• HLA-DRB1 Chains
• ErbB Receptors

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects)
• Drug Eruptions (etiology, genetics, immunology)
• ErbB Receptors (antagonists & inhibitors)
• Exanthema (chemically induced, genetics, immunology)
• Female
• Genetic Predisposition to Disease
• HLA Antigens (genetics)
• HLA-A Antigens (genetics)
• HLA-B Antigens (genetics)
• HLA-C Antigens (genetics)
• HLA-DRB1 Chains (genetics)
• Humans
• Male
• Middle Aged
• Neoplasms (drug therapy, genetics, immunology)
• Polymorphism, Genetic
• Prognosis