Gefitinib

• 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.