What is the recommended dose of Gefitinib (Iressa) for non-small cell lung cancer?

Gefitinib Dosing for Non-Small Cell Lung Cancer

The recommended dose of gefitinib for non-small cell lung cancer is 250 mg orally once daily until disease progression or unacceptable toxicity. 1

Patient Selection and Indications

Gefitinib is indicated for:

• First-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations 1
• Second-line and subsequent therapy for selected symptomatic patients who are not candidates for chemotherapy and for whom erlotinib is not available 2

Patient Selection Process:

1. Test for EGFR mutations in tumor or plasma specimens
2. If mutations are not detected in plasma, test tumor tissue if feasible
3. Select patients with confirmed EGFR exon 19 deletions or exon 21 L858R mutations

Administration Guidelines

• Take with or without food 1
• Do not take a missed dose within 12 hours of the next dose 1
• For patients who have difficulty swallowing:
  • Immerse tablet in 4-8 ounces of water
  • Stir for approximately 15 minutes
  • Drink immediately or administer through nasogastric tube
  • Rinse container with additional 4-8 ounces of water and drink/administer 1

Dose Modifications

For Adverse Reactions:

Withhold gefitinib (for up to 14 days) for:

• Acute onset/worsening pulmonary symptoms (dyspnea, cough, fever)
• Grade 2+ ALT/AST elevations
• Grade 3+ diarrhea
• Severe/worsening ocular disorders including keratitis
• Grade 3+ skin reactions 1

Resume treatment when adverse reaction resolves or improves to Grade 1.

Permanently discontinue for:

• Confirmed interstitial lung disease (ILD)
• Severe hepatic impairment
• Gastrointestinal perforation
• Persistent ulcerative keratitis 1

For Drug Interactions:

• Increase to 500 mg daily when co-administered with strong CYP3A4 inducers
• Resume 250 mg dose seven days after discontinuation of the CYP3A4 inducer 1

Efficacy and Safety Considerations

Efficacy:

• Response rates are higher in:
  • Female patients
  • Patients with adenocarcinoma histology
  • Never-smokers
  • Asian ethnicity 2

Safety Profile:

• Most common adverse effects: rash, diarrhea, acne, dry skin, nausea, and vomiting 3
• Most adverse effects are mild-to-moderate and don't require discontinuation 3
• Interstitial lung disease occurs in approximately 1% of patients worldwide (2% in Japanese patients) and is fatal in about one-third of cases 3

Alternative Dosing Considerations

Reduced dose gefitinib (250 mg alternate day) may be considered for patients experiencing significant adverse effects:

• Studies suggest comparable progression-free survival between standard and reduced dose in patients who required dose reduction due to toxicity 4
• In the NEJ002 study, patients who reduced their gefitinib dose due to toxicities showed no inferior outcomes compared to those who maintained standard dosing 5

Important Clinical Considerations

• Gefitinib does not commonly cause myelosuppression or alopecia, which are typical adverse effects of chemotherapy 3
• Regular liver function monitoring is required due to potential hepatotoxicity 1
• No clinical studies have definitively demonstrated a correlation between EGFR expression and response to gefitinib 6

Remember that patient selection based on EGFR mutation status is critical for optimal treatment outcomes with gefitinib.