- 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.