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


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.
Tan
A R
AR
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Steinberg
S M
SM
Parr
A L
AL
Nguyen
D
D
Yang
S X
SX
D017486:Acneiform Eruptions / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology / Q000556:secondary; D003875:Drug Eruptions / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005499:Folliculitis / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
D000970:Antineoplastic Agents; D015415:Biomarkers; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases