EGF Ointment for Erlotinib Skin Lesion

Erlotinib

Advances in the knowledge of tumor biology and mechanisms of oncogenesis has granted the singling out of several molecular targets for NSCLC treatment. Among these targets, epidermal growth factor receptor (EGFR), or HER1, has received particular attention in lung cancer treatment. EGFR is a transmembrane receptor found primarily on cells of epithelial origin. Autophosphorylation of its intracellular domain initiates a cascade of events leading to cell proliferation. EGFR is commonly expressed at a high level in a variety of solid tumors and it has been implicated in the control of cell survival, proliferation, metastasis and angiogenesis. The main pharmacological strategies in clinical development for therapeutic inhibition of EGFR are monoclonal antibodies to antagonize ligand-receptor binding, and small-molecules to inhibit tyrosine kinase domain activation. The main EGFR inhibitors are cetuximab, an anti-EGFR monoclonal antibody, and Erlotinib an EGFRtyrosine kinase inhibitor. The key indications for clinical use are colorectal cancer and head and neck cancer for cetuximab and NSCLC for Erlotinib. Erlotinib, a quinazolin-4-amine, is a highly potent, orally available, reversible inhibitor of EGFR tyrosine kinase. Erlotinib, in a phase III randomized placebo-controlled trial, has been proven to prolong survival (6.7 months versus 4.7 months for Erlotinib and for placebo respectively, p = 0.001) in NSCLC patients after first or second line chemotherapy. The analysis of quality of life and time to deterioration of patients reported symptoms showed statistically and clinically meaningful benefit for patients randomized to Erlotinib. Moreover, Erlotinib resulted active (response rate of 8.9%) and safe (only 5% of patients discontinued treatment for toxicity). Following this trial, Erlotinib has been approved by Food and Drug Administration and Committee for Medicinal Products for Human use in chemotherapy-pretreated advanced NSCLC. Skin rash is a common side-effect of all HER1/EGFR inhibitors.

EGF ointment

Rash affecting the skin above the waist, is the most common adverse event associated with Erlotinib, and generally develops within 7-10 days of starting treatment. Skin rash may spontaneously resolve and reappear and it is reversible following drug discontinuation. However, when it develops, this chronic side-effect is very distressing for the patient. The increasing use of EGFR-targeted agents and specifically of Erlotinib in NSCLC treatment, and simultaneously the lack of clinical trials on this topic, makes rash management and etiology investigation high priorities.

It has been reported that repeated treatment with EGF increases the epithelial cell proliferation in a dose dependent manner and accelerates the wound healing process, whereas a single EGF treatment has no noticeable effect on the wound-healing rate. There have been many studies aimed at developing a topical formulation with the sustained and stable pharmacological properties of recombinant human EGF (rhEGF). And the rh-EGF concentration between 1 and 5 ug/g can be seen as the ideal concentration to achieve the most efficient results for acute wounds with partial thickness defects.