Epidermal growth factor receptor inhibitors

Induce apoptosis, cell cycle arrest and tumor growth inhibition.

Two classes: humanized monoclonal antibodies against the extra cellular, ligand-binding domain of the receptor, and small molecular tyrosine kinase inhibitors that complete with the intracellular adenosine triphosphate binding domain of the receptor.

Include monoclonal antibodies cetuximab and panitumubab, and tyrosine kinase inhibitors erlotinib, geftinib and lapatinib.

Erlotinib and geftinib are highly specific for EGFR and/or reversible inhibitors, meeting they can be competed off the receptor by adenosine try phosphate.

Later degeneration EGFR inhibitors such as afatinib are irreversibly bound to the receptor forming a covalent bond inside the cell between the drug and the receptor.

Clinical trials in EGFR-mutant patients demonstrate EGFR inhibitors have a response rate of approximately 70%.

Patients with EGFR-mutant lung cancers should be treated up front with EGFR inhibitors rather than chemotherapy as randomized trials show this improves progression free survival and quality of life.

Have a favorable toxicity profile.

Toxicities primarily cutaneous, especially papulopustular eruption, described as acneform rashes.

Almost 100% of patients treated with EGFRI have cutaneous adverse effects.

Epithelial growth factor receptor inhibitor rash is dose dependent.

Epithelial growth factor receptor inhibitor cutaneous toxicity may be positively correlated with clinical response to treatment.

EGFRI skin toxicity is mild in most cases.

Not associated with death.

Rash the cause of treatment cessation or dose modification in 8-17% of patients on EGFR inhibitors.

EGFR inhibitors associated with 12-16% incidence of paronychia or peri-nail inflammation, xerosis 7-35%, nail changes 10-29 %, pruritus 11%, hair changes 9%, mucosisits 2-36%, hand-foot reactions 10-62%, and hypersensitivity reactions 2-3%.

Both classes associated with popular and pustular acne-like rash that affects mainly the face, scalp and upper torso.

Grade 3 rash seen in 5-18% of patients and breaks in treatment and dose reduction often needed to control symptoms.

Rash typically develops within 1-3 weeks and consists of a nonpruritic folliculitis or pustular eruption primarily on the face, trunk and occasionally the upper extremities.

Approximately 88% of patients receiving these agents develop a rash within the first two weeks of starting treatment, and the rash appears to be dose dependent.

Patients with rash commonly experience pruritus and pain.

Epidermal growth factor receptor inhibitor rash biopsies show lymphocytic perifolliculitis or supppurative superficial folliculitis without infection.

Epidermal growth factor receptor inhibitor papulopustular eruption may be a surrogate marker for the drugs efficacy with a positive correlation between the rash and tumor response, survival or both.

Adverse effects on eyes include conjunctivitis and keratoconjunctivitis sicca in 12-14% of patients.

Cetuximab, gefitinib, panitumubab and erlotinib.

Mutations of the EGFR gene have been exclusively found in a subset of pulmonary adenocarcinomas highly sensitive to tyrosine kinase inhibitors for EGFR.

The presence of EGFR mutations an indicator of clinical efficacy of tyrosine kinase inhibitors (TKI) in patients with metastatic or recurrent NSCLC.

Prophylaxis with minocycline may be useful to decreases severity of the rash (Scope).

Management of epidermal growth factor receptor inhibitor rash includes oral and topical antibiotics, systemic or topical corticosteroids, topical retinoids, and anti-histamines.

Regenecare, a topical wound gel with lidocaine, collagen, vitamin E, aloe vera is and effective in relieving itching in patients with EGFRIs (Wong SF).

Resistance occurs 9-15 months after the start of therapy.

Resistance to EGFR inhibitors is cause 50-60% of time due to a single mutation T790M that arises in the EGFR itself

If a tumor acquires T790M mutation EGFR inhibitors are unable to be beneficial.

Despite favorable responses to TKI inhibitors EGFR mutant tumors sustain progression by 1 year, mostly due to the development of resistant mutations.

In addition to targeting mutant EGFR in tumor cells these inhibitors inhibit wild type EGFR residing in normal, healthy tissues such as the skin and lining of the GI tract.

Second-generation EGFR inhibitors have more rash and diarrhea due to the fact they are irreversible bound agents.

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