- Class: Tyrosine kinase inhibitor – EGFR inhibitor (small molecule, reversible)
Mechanism of Action (MOA)
- Inhibits EGFR tyrosine kinase by binding the ATP-binding site.
- Blocks downstream signaling (RAS/RAF/MEK/ERK, PI3K/AKT).
- Leads to cell cycle arrest, reduced proliferation, and apoptosis in EGFR-dependent tumors.
Clinical Uses
- Non-small cell lung cancer (NSCLC) – advanced/metastatic EGFR-mutated tumors (exon 19 deletions, exon 21 L858R).
- Used primarily as first-line therapy for EGFR-mutant NSCLC.
Dosing (Adults)
- 250 mg orally once daily, on an empty stomach (≥1 hour before or 2 hours after meals).
- Dose adjustments may be needed in:
- Severe hepatic impairment
- Drug interactions (strong CYP3A4 inhibitors/inducers).
Toxicities
- Dermatologic: Acneiform rash, dry skin, pruritus.
- Diarrhea – mild to moderate, can rarely be severe.
- Fatigue, anorexia, nausea.
- Hepatotoxicity – monitor liver enzymes.
- Interstitial lung disease (rare but serious).
- Ocular toxicity: keratitis, conjunctivitis (rare).
Monitoring
- Skin: prophylaxis and treatment of rash as needed.
- Liver function tests.
- GI symptoms: monitor and manage diarrhea.
- Pulmonary symptoms: watch for signs of ILD.
- Drug interactions: CYP3A4 substrates/inhibitors/inducers.
Summary
Gefitinib (Iressa®) is a reversible EGFR TKI used in first-line treatment of EGFR-mutated NSCLC. Main concerns are skin rash, diarrhea, hepatotoxicity, and rare ILD, with strict adherence to empty stomach administration and attention to CYP3A4 interactions.