Gefitinib

Summary

Gefitinib is a targeted therapy drug widely used to treat advanced non-small cell lung cancer (NSCLC) with specific mutations in the epidermal growth factor receptor (EGFR). This article explores the mechanism of action, indications, dosage, precautions, side effects, cost considerations, and alternative medicines. 

We also dive into how gefitinib works, its metabolism, and important resistance factors related to EGFR mutations. This guide aims to provide patients, caregivers, and healthcare professionals with comprehensive and up-to-date information on gefitinib for optimal treatment outcomes.

Introduction to Gefitinib 

Gefitinib is an oral anticancer drug classified under tyrosine kinase inhibitors (TKIs) that selectively inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase. Manufactured originally by AstraZeneca and marketed under brand names such as Iressa and Getinib which is manufactured by Drug International Ltd., a Bangladeshi pharmaceuticals company, gefitinib has revolutionized the treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) harboring specific EGFR mutations.

Non-small cell lung cancer accounts for approximately 85% of lung cancer cases worldwide. The discovery of EGFR mutations as a driving factor in tumor growth has paved the way for targeted therapies like gefitinib, offering better survival rates and quality of life compared to traditional chemotherapy.

What is Gefitinib?

Gefitinib (brand names include Iressa and Getinib) is an oral anticancer medication developed by AstraZeneca. It belongs to the class of drugs called tyrosine kinase inhibitors (TKIs) and is primarily used to treat advanced non-small cell lung cancer (NSCLC). NSCLC tumors often harbor mutations in the epidermal growth factor receptor (EGFR), a protein that drives cancer cell growth and proliferation. Gefitinib blocks this receptor, slowing down or stopping tumor progression.

Gefitinib Mechanism of Action 

Gefitinib acts by selectively inhibiting the tyrosine kinase domain of the EGFR protein. EGFR is a cell surface receptor involved in signaling pathways that regulate cell proliferation, survival, and metastasis. Tumors with EGFR activating mutations lead to uncontrolled signaling, promoting cancer growth.

By binding to the ATP-binding site of the receptor’s tyrosine kinase, gefitinib blocks phosphorylation and downstream signaling cascades such as the PI3K/AKT and RAS/RAF/MEK pathways. This inhibition results in:

• Decreased tumor cell proliferation
• Induced apoptosis (programmed cell death)
• Reduced angiogenesis (formation of new blood vessels feeding the tumor)

 

Key Points of Gefitinib Mechanism of Action

Feature	Description
Drug class	EGFR tyrosine kinase inhibitor (TKI)
Target receptor	Epidermal Growth Factor Receptor (EGFR)
Binding site	ATP-binding pocket of EGFR tyrosine kinase domain
Effect on tumor cells	Inhibits proliferation and induces apoptosis
Impact on signaling pathways	Blocks PI3K/AKT and RAS/RAF/MEK cascades

Indications and Uses 

Gefitinib is FDA-approved for the treatment of:

• Advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations confirmed by an FDA-approved test.
• Patients who have not received prior chemotherapy for metastatic disease.

It is particularly effective in tumors that exhibit EGFR mutation-positive status, representing about 10-15% of NSCLC cases in Western populations and up to 40% in Asian populations.

Dosage and Administration 

Standard Dose: Gefitinib is commonly prescribed as 250 mg tablets taken once daily.

Administration: It is an oral medication, taken with or without food, at the same time each day.

Dose Adjustments: May be needed in cases of liver impairment or severe side effects.

Treatment Duration: Usually continued until disease progression or unacceptable toxicity occurs.

Important Administration Notes:

• Tablets should be swallowed whole with water.
• Missed doses should be taken as soon as remembered but not doubled.
• Regular monitoring via CT scans and blood tests is essential to evaluate effectiveness and toxicity.

Precautions and Contraindications 

Before initiating gefitinib therapy, several precautions must be considered:

• Liver impairment: Dose adjustment may be required due to hepatic metabolism.
• Interstitial lung disease (ILD): Patients with pre-existing ILD are at higher risk for severe lung toxicity.
• Pregnancy and breastfeeding: Gefitinib is contraindicated during pregnancy due to potential fetal harm.
• Drug interactions: Concomitant use with CYP3A4 inducers or inhibitors may alter gefitinib metabolism.

Gefitinib and EGFR Mutation in NSCLC

Understanding the relationship between EGFR mutations and gefitinib response is crucial for effective treatment.

• EGFR Mutation Testing: Mandatory before therapy to identify patients likely to benefit.
• Common Mutations: Exon 19 deletions and exon 21 L858R point mutations.
• Resistance Mechanisms: Secondary mutations like T790M or MET amplification reduce gefitinib efficacy.
• Erlotinib vs. Gefitinib: Both are EGFR TKIs, but differ slightly in side effect profiles and FDA approvals.

Side Effects and Precautions

Gefitinib is generally well tolerated but has notable side effects that require monitoring.

Common Side Effects

Side Effect	Frequency	Notes
Diarrhea	Very common	Manage with hydration and meds
Rash/Acne-like eruptions	Very common	Can affect quality of life
Nausea	Common	Usually mild
Fatigue	Common	May require dose adjustment

Serious but Rare Side Effects

• Interstitial lung disease (ILD)
• Liver toxicity (monitor liver enzymes)
• Severe skin reactions
• Eye problems (dry eye, keratitis)

Precautions

• Patients with pre-existing lung disease should be closely monitored.
• Liver function tests should be performed regularly.
• Inform your doctor about all medications to avoid drug interactions.

Does Medicare Cover Gefitinib?

Medicare typically covers gefitinib under Medicare Part D (prescription drug coverage) if prescribed by a licensed oncologist. However, coverage may depend on specific plan formularies and patient eligibility.

Resistance and EGFR Mutation in NSCLC 

Despite initial responsiveness, many patients develop resistance to gefitinib, often within 9-14 months. Common mechanisms of resistance include:

• Secondary EGFR mutations such as T790M mutation
• Activation of alternative signaling pathways (MET amplification)
• Phenotypic transformation (small cell lung cancer transformation)

Understanding and detecting these resistance mechanisms are critical for optimizing treatment strategies, including switching to second-generation EGFR TKIs like osimertinib or combining with chemotherapy.

Cost, Insurance, and Availability

• Cost of Gefitinib: The price varies globally; generic versions like Getinib are more affordable.
• Medicare Coverage: Medicare may cover gefitinib under Part D prescription plans, but co-payments and coverage details vary.
• Online Purchase: Gefitinib 250 mg tablets can be purchased online through licensed pharmacies with prescriptions.
• Manufacturer: Originally developed by AstraZeneca; generics are now widely available.

Alternative Medicines and Brands 

Several alternative EGFR TKIs and gefitinib brand names are available globally:

Brand Name	Manufacturer	Drug Class	Typical Use
Iressa	AstraZeneca	EGFR TKI	Gefitinib original branded drug
Getinib	Various Generics	EGFR TKI	Generic gefitinib
Erlotinib	Genentech/Roche	EGFR TKI	Alternative first-line treatment
Afatinib	Boehringer Ingelheim	Second-generation EGFR TKI	Used for some resistant mutations
Osimertinib	AstraZeneca	Third-generation EGFR TKI	Effective in T790M resistance

Patient Advice and Supportive Care 

• Adherence: Take medication consistently at the same time daily.
• Monitor side effects: Report skin rash or breathing difficulties promptly.
• Lifestyle: Maintain a balanced diet and engage in mild exercises like walking to support overall health.
• Follow-up: Regular scans and blood tests are vital for monitoring treatment response and toxicity.
• Psychological support: Consider counseling or support groups to cope with cancer diagnosis and treatment stress.

Conclusion 

Gefitinib has transformed the treatment approach for advanced NSCLC patients harboring EGFR mutations. With its targeted mechanism of action, relatively manageable side effect profile, and proven efficacy, it remains a cornerstone in precision oncology. Understanding the drug’s usage, potential side effects, cost factors, and resistance patterns empowers patients and healthcare providers to optimize therapy and improve survival outcomes.

FAQs

Q1: What is gefitinib used for?

A: Gefitinib is used to treat advanced non-small cell lung cancer with specific EGFR mutations. It inhibits tumor growth by blocking the EGFR tyrosine kinase.

Q2: How does gefitinib work?

A: Gefitinib blocks the EGFR signaling pathway that promotes cancer cell proliferation and survival by inhibiting the receptor’s tyrosine kinase activity.

Q3: What are the common side effects of gefitinib?

A: Common side effects include skin rash, diarrhea, fatigue, and elevated liver enzymes. Rare but serious side effects include interstitial lung disease.

Q4: Can I buy gefitinib 250 mg tablets online?

A: Yes, gefitinib 250 mg tablets are available for online purchase through licensed pharmacies, but a prescription is mandatory to ensure safe and legitimate use.

Q5: Does Medicare cover gefitinib treatment?

A: Medicare typically covers gefitinib under Part D prescription drug plans, depending on the plan’s formulary and patient eligibility.