Gefitinib

Primary Uses

Gefitinib is used to treat metastatic non-small cell lung cancer (NSCLC). This is a form of lung cancer that has progressed and spread beyond the lungs to other organs or tissues.

Specific Patient Requirements

This medication is not used for all types of lung cancer. It is specifically intended for patients whose tumors have certain abnormal epidermal growth factor receptor (EGFR) genes. These genetic markers include:

• Exon 19 deletions
• Exon 21 (L858R) substitution mutations

A healthcare professional will perform a specific test on a sample of the tumor to determine if these mutations are present before prescribing gefitinib. It is often used as a first-line treatment for patients who meet these genetic criteria.

Mechanism of Action

Gefitinib belongs to a class of medications known as tyrosine kinase inhibitors (TKIs). It is designed to target a specific protein called the epidermal growth factor receptor (EGFR), which is found on the surface of both normal and cancer cells.

In certain types of non-small cell lung cancer, the EGFR protein is mutated or overactive. This sends continuous signals to the cancer cells, telling them to grow, divide, and spread throughout the body. Gefitinib works by:

• Binding to the EGFR protein inside the cancer cells.
• Blocking the chemical signals that trigger cell division.
• Interfering with the pathways that allow tumors to survive and grow.

Because gefitinib specifically targets these proteins, it is considered a targeted therapy. It is primarily used for cancers that have specific genetic markers, such as exon 19 deletions or exon 21 substitution mutations. These mutations are typically identified through laboratory testing of the tumor tissue before treatment begins.

Common Side Effects

Many people taking gefitinib experience mild to moderate side effects. These may include:

• Diarrhea
• Skin rash or acne-like breakouts
• Dry, itchy, or peeling skin
• Nausea and vomiting
• Loss of appetite and weight loss
• Mouth sores
• Weakness or lack of energy
• Nail changes, such as redness or swelling around the fingernails or toenails

Serious Side Effects

While less common, some side effects can be severe and require immediate medical attention. Contact a healthcare provider right away if you experience:

• Lung problems: New or worsening shortness of breath, cough, or fever.
• Liver issues: Yellowing of the eyes or skin, dark-colored urine, or pain in the upper right side of the stomach.
• Severe skin reactions: Severe rash, blistering, or peeling of the skin.
• Eye problems: Blurred vision, eye pain, redness, or increased sensitivity to light.
• Severe digestive issues: Persistent or severe diarrhea that leads to dehydration.
• Signs of an allergic reaction: Hives, swelling of the face or throat, or difficulty breathing.

Lung Inflammation

Interstitial lung disease (ILD) is a serious and potentially fatal side effect associated with gefitinib. Treatment is typically withheld if a patient develops new or worsening respiratory symptoms, such as shortness of breath, cough, or fever. If ILD is confirmed, the medication is usually discontinued permanently.

Liver Function

Gefitinib can cause significant increases in liver enzymes. Healthcare providers monitor liver function through blood tests before starting the drug and at regular intervals during treatment. Changes in dose or stopping the medication may be required if liver enzyme levels become too high.

Gastrointestinal Complications

• Severe Diarrhea: This can lead to dehydration and may require medical intervention or a pause in treatment.
• Gastrointestinal Perforation: Although rare, holes in the wall of the digestive tract have been reported in patients taking this medication.

Ocular and Skin Disorders

Inflammation of the cornea (keratitis), corneal erosion, and other eye problems can occur. Patients experiencing eye pain, redness, or vision changes should seek medical evaluation. Additionally, severe skin conditions involving blistering or peeling have been reported and require immediate attention.

Drug Interactions

Certain medications, including proton pump inhibitors (used for stomach acid) and strong CYP3A4 inducers or inhibitors, can change the levels of gefitinib in the blood. This may affect how well the drug works or increase the risk of side effects.

Pregnancy and Breastfeeding

Based on its mechanism of action, gefitinib can cause fetal harm. It is recommended that individuals of reproductive potential use effective contraception during treatment and for at least two weeks after the last dose. Breastfeeding is not recommended during therapy.

Pregnancy

Gefitinib can cause harm to an unborn baby if taken during pregnancy. Animal studies have indicated that the medication may lead to decreased fetal weight and an increased risk of death in newborns. While there is limited data on the effects of gefitinib in pregnant humans, the way the drug works suggests it could interfere with normal fetal development.

Individuals who are able to become pregnant should discuss the risks with their healthcare provider. It is generally recommended to use effective contraception during treatment and for at least two weeks after the final dose of gefitinib. If a patient becomes pregnant while taking this medication, they should notify their doctor immediately.

Breastfeeding

It is not known whether gefitinib passes into human breast milk. Due to the potential for serious side effects in a breastfeeding infant, healthcare providers typically advise against breastfeeding while taking this medication. Patients should consult with their medical team to discuss the best way to feed their infant during treatment.

Dosage Forms

Gefitinib is available as a film-coated tablet. It is an oral medication that is typically swallowed whole and can be taken with or without food.

FDA Approval Status

Gefitinib is approved by the U.S. Food and Drug Administration (FDA) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC). Its use is specifically indicated for patients whose tumors have certain epidermal growth factor receptor (EGFR) mutations, specifically exon 19 deletions or exon 21 (L858R) substitution mutations.

The FDA requires that these mutations be confirmed using an FDA-approved diagnostic test before a patient begins treatment with this medication.

Regulatory History

The regulatory status of gefitinib has changed significantly since its introduction:

• It was first granted accelerated approval by the FDA in 2003.
• In 2005, the FDA restricted its use to patients who were already participating in clinical trials or who had previously benefited from the drug, after larger studies failed to show a survival benefit in the general population.
• In 2015, the FDA issued a new approval for gefitinib as a first-line treatment specifically for patients with the identified EGFR mutations.

Safety and Monitoring

There are currently no Boxed Warnings or Risk Evaluation and Mitigation Strategy (REMS) requirements for gefitinib. The FDA-approved labeling includes pharmacogenomic information, which emphasizes the importance of biomarker testing to identify patients who are most likely to respond to the therapy.

FDA-Approved Indications

The U.S. Food and Drug Administration (FDA) has approved gefitinib for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC). This approval is specifically for patients whose tumors have certain epidermal growth factor receptor (EGFR) mutations, as detected by an FDA-approved test.

The specific genetic markers targeted by this medication include:

• Exon 19 deletions
• Exon 21 (L858R) substitution mutations

Testing Requirements

The FDA requires that the presence of these specific EGFR mutations be confirmed using a validated diagnostic test before starting treatment. Gefitinib is not indicated for use in patients whose tumors do not harbor these specific mutations, as its safety and efficacy have not been established for the general lung cancer population.

Regulatory History

Gefitinib was originally granted accelerated approval by the FDA in 2003. However, after subsequent clinical trials failed to demonstrate a survival benefit in the general patient population, its use was restricted for several years. In 2015, the FDA issued a new approval for gefitinib as a targeted first-line therapy for the specific subset of patients with EGFR-positive metastatic NSCLC.