Erlotinib

• Class: Tyrosine kinase inhibitor – EGFR inhibitor (small molecule, reversible)

Mechanism of Action (MOA)

• Binds the ATP-binding site of EGFR tyrosine kinase → inhibits autophosphorylation.
• Blocks downstream signaling pathways (RAS/RAF/MEK/ERK, PI3K/AKT).
• Results in inhibition of cell proliferation, angiogenesis, and survival, and induces apoptosis in EGFR-dependent tumors.

Clinical Uses

• Non-small cell lung cancer (NSCLC) – advanced or metastatic with EGFR activating mutations (exon 19 deletions or exon 21 L858R).
• Pancreatic cancer – in combination with gemcitabine (locally advanced or metastatic).

Dosing (Adults)

• NSCLC: 150 mg orally once daily (on empty stomach, ≥1 hour before or 2 hours after meals).
• Pancreatic cancer: 100 mg orally once daily in combination with gemcitabine.
• Dose adjustments:
  • Hepatic impairment – reduce if Child-Pugh B/C.
  • Drug interactions – strong CYP3A4 inhibitors/inducers can require dose modification.

Toxicities

• Dermatologic: Acneiform rash (correlates with efficacy), dry skin, pruritus.
• Diarrhea – mild to moderate; rarely severe.
• Fatigue, anorexia, nausea.
• Hepatotoxicity – monitor LFTs.
• Interstitial lung disease (rare but serious).
• Ocular toxicity: keratitis, conjunctivitis (rare).

Monitoring

• Skin: manage rash with topical steroids, antibiotics if needed.
• Liver function tests.
• GI toxicity: diarrhea management and hydration.
• Pulmonary symptoms: monitor for ILD (dyspnea, cough).
• Drug interactions: CYP3A4 substrates/inhibitors/inducers.

Summary

Erlotinib (Tarceva®) is a reversible EGFR tyrosine kinase inhibitor used in EGFR-mutated NSCLC and pancreatic cancer with gemcitabine. Key concerns are skin rash, diarrhea, hepatotoxicity, and rare ILD, with important food and drug interaction considerations.