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Annals of Oncology Advance Access published online on September 17, 2007
Annals of Oncology, doi:10.1093/annonc/mdm444
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© 2007 European Society for Medical Oncology

Markers in the epidermal growth factor receptor pathway and skin toxicity during erlotinib treatment

A. R. Tan1,{dagger}, S. M. Steinberg2, A. L. Parr3, D. Nguyen3 and S. X. Yang3,*

1 Medical Oncology Branch, Center for Cancer Research
2 Biostatistics and Data Management Section, Center for Cancer Research
3 National Clinical Target Validation Laboratory, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA

* Correspondence to: Dr S. X. Yang, National Clinical Target Validation Laboratory, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 37 Convent Drive, Building 37, Room 1048A, Bethesda, MD, USA. Fax: +1-301-480-4679; E-mail: xy32m{at}nih.gov

Background: Skin toxicity is a common adverse effect of erlotinib and other anti-epidermal growth factor receptor (EGFR) agents. The aim of the study was to explore the relationship between markers in the EGFR pathway and skin rash.

Patients and methods: Eighteen patients with metastatic breast cancer were treated with daily oral erlotinib at 150 mg. Skin biopsies were obtained at baseline and after 1 month of treatment in 15 patients. EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated Akt (pAkt) or Ki67 were examined quantitatively by immunohistochemistry.

Results: 11 of 18 (61%, 95% confidence interval 35.7% to 82.7%) patients developed skin rash. pAkt at baseline was significantly higher in patients with no rash than those with a grade 1 or 2 rash (18.8 ± 8.3 versus 2.4 ± 1.2 versus 3.3 ± 3.3; P = 0.0017 for trend). There was a trend towards a significant increase of pMAPK in skin posttreatment with increasing grade of rash (no rash versus grade 1 versus grade 2 rash: 4.5 ± 2.3 versus 8.4 ± 4.2 versus 19.4 ± 4.6; P = 0.036). Other markers were not associated with rash.

Conclusions: pAkt was significantly associated with not developing a rash and may have a predictive utility for skin toxicity in patients treated with erlotinib and possibly with other anti-EGFR agents.

EGFR pathway markers, erlotinib, skin toxicity

{dagger} Present address: The Cancer Institute of New Jersey, New Brunswick, NJ, USA

Received for publication June 15, 2007. Accepted for publication August 10, 2007.


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