Erlotinib

• Non-Small Cell Lung Cancer (NSCLC)
• Pancreatic Cancer
• EGFR-Mutated Lung Cancer
• Targeted Cancer Therapy

Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer. This oral targeted therapy provides benefit for patients whose tumors harbor EGFR mutations or overexpression.

Mechanism of Action

Erlotinib reversibly inhibits the intracellular tyrosine kinase domain of the epidermal growth factor receptor (EGFR/HER1/ErbB-1). EGFR is a transmembrane glycoprotein that, when activated by ligand binding, triggers intracellular signaling cascades including the RAS-RAF-MEK-ERK and PI3K-AKT pathways, promoting cell proliferation, survival, and metastasis. In many cancers, EGFR is overexpressed or mutated, leading to constitutive activation. By blocking EGFR tyrosine kinase activity, erlotinib inhibits downstream signaling, inducing cell cycle arrest and apoptosis. Activating EGFR mutations (exon 19 deletions, L858R) predict sensitivity to erlotinib.

Available Formulations

Erlotinib is available as film-coated tablets in 25 mg, 100 mg, and 150 mg strengths. The tablets should be taken on an empty stomach, at least 1 hour before or 2 hours after food intake, as food substantially increases absorption. The medication should be taken at approximately the same time each day.

Medical Uses

Erlotinib is FDA-approved for first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, maintenance treatment of patients with locally advanced or metastatic NSCLC without progression after four cycles of platinum-based chemotherapy, and first-line treatment of locally advanced, unresectable or metastatic pancreatic cancer in combination with gemcitabine. For NSCLC, EGFR mutation testing is required before prescribing for first-line treatment.

Dosing Guidelines

For NSCLC, the recommended dose is 150 mg once daily on an empty stomach. For pancreatic cancer, the dose is 100 mg once daily in combination with gemcitabine. Treatment continues until disease progression or unacceptable toxicity. Dose reductions are available for toxicity management (50 mg decrements). Concurrent smoking significantly reduces erlotinib exposure; higher doses may be considered in current smokers, with dose reduction upon smoking cessation.

Important Safety Information

Serious and sometimes fatal interstitial lung disease (ILD)/pneumonitis has occurred; treatment should be interrupted if ILD is suspected and discontinued if confirmed. Hepatotoxicity, including hepatic failure and hepatorenal syndrome, has been reported; liver function tests should be monitored. Renal failure, including fatalities, has occurred, especially with concurrent NSAID use and dehydration. GI perforations have been reported. Patients should use sunscreen and avoid sun exposure due to photosensitivity. Corneal perforation and ulceration have occurred.

Drug Interactions

Strong CYP3A4 inducers (rifampin, phenytoin, carbamazepine, St. John's Wort) significantly reduce erlotinib levels; consider alternative agents or dose increase (with careful monitoring). Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) increase erlotinib levels. Proton pump inhibitors and H2 blockers reduce absorption significantly; avoid concurrent use or separate dosing. Warfarin may have enhanced effect; monitor INR closely.

Special Populations

Erlotinib may cause fetal harm; women of reproductive potential should use effective contraception during treatment and for at least 1 month after the last dose. Males with female partners of reproductive potential should use contraception during treatment and for 1 week after. It is unknown whether erlotinib is excreted in human breast milk; breastfeeding is not recommended. Safety and efficacy have not been established in pediatric patients. Elderly patients showed no overall differences in safety or efficacy. No dose adjustment is needed for renal impairment. Use with caution in hepatic impairment; dose reduction may be necessary.