What is Gefitinib used for?

Gefitinib, commonly known under the trade name Iressa, is a small-molecule tyrosine kinase inhibitor (TKI) that has been a groundbreaking advancement in the treatment of non-small cell lung cancer (NSCLC). Gefitinib targets the epidermal growth factor receptor (EGFR), a protein that, when mutated, can promote the growth of cancer cells. This drug has been developed primarily for patients who exhibit specific types of EGFR mutations. Research institutions and pharmaceutical companies have collaborated extensively to bring Gefitinib to clinical use, and it has proven to be particularly effective in certain subsets of lung cancer patients.

Approved by the U.S. Food and Drug Administration (FDA) and other regulatory bodies around the world, Gefitinib is indicated for the first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. Research and clinical trials have shown that patients with these specific mutations respond better to Gefitinib compared to traditional chemotherapies, making it a tailored, precision medicine approach. Ongoing studies are exploring its efficacy in combination with other treatments and in different types of cancers.

The mechanism of action of Gefitinib revolves around its ability to inhibit the tyrosine kinase activity of the EGFR. EGFR is a transmembrane receptor with an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyrosine kinase domain. When EGFR binds to its natural ligands, such as epidermal growth factor (EGF), it undergoes dimerization and autophosphorylation of tyrosine residues within the intracellular domain. This activation triggers a cascade of downstream signaling pathways, including the RAS-RAF-MEK-ERK and PI3K-AKT pathways, which promote cell proliferation, survival, and differentiation.

Gefitinib binds to the ATP-binding site of the EGFR tyrosine kinase domain, thereby preventing the phosphorylation of tyrosine residues and subsequent activation of downstream signaling pathways. By inhibiting these pathways, Gefitinib effectively suppresses the growth and proliferation of cancer cells harboring EGFR mutations. The presence of specific EGFR mutations, such as exon 19 deletions and exon 21 L858R substitutions, increases the sensitivity of tumors to Gefitinib, making it a highly targeted therapy for patients with these genetic alterations.

Gefitinib is administered orally in the form of tablets, with a recommended dosage of 250 mg once daily. It can be taken with or without food, offering flexibility for patients in their daily routines. The onset of action can vary among individuals, but clinical studies have shown that patients may experience therapeutic effects within a few weeks of starting treatment. However, it is essential to continue taking the medication as prescribed by a healthcare provider, even if symptoms improve, to ensure sustained control of the disease.

Patients are advised to swallow the tablets whole with a glass of water and should avoid crushing or chewing them. In cases where patients have difficulty swallowing tablets, the tablet can be dispersed in a glass of water (non-carbonated). No other liquids should be used, and the water should be stirred until the tablet is dispersed entirely and then consumed immediately. The glass should be rinsed with an additional half glass of water, and this should also be drunk to ensure the full dose is ingested.

Like all medications, Gefitinib is associated with a range of side effects, some of which can be severe. Common side effects include diarrhea, rash, acne, dry skin, nausea, vomiting, and loss of appetite. These symptoms are generally manageable and often diminish as the body adjusts to the medication. However, patients should be monitored closely, and any persistent or worsening symptoms should be reported to the healthcare provider promptly.

More serious side effects include interstitial lung disease (ILD), liver function abnormalities, and gastrointestinal perforation. ILD, although rare, can be life-threatening and presents with symptoms such as difficulty breathing, cough, and fever. Liver function abnormalities can manifest as jaundice, dark urine, and fatigue, indicating that liver enzymes should be regularly monitored during treatment. Gastrointestinal perforation, though extremely rare, requires immediate medical attention if patients experience severe abdominal pain.

Contraindications for Gefitinib include patients with a history of severe hypersensitivity to the drug or any of its components. It is also contraindicated in pregnant or breastfeeding women due to the potential risk to the fetus or infant. Caution is advised in patients with preexisting liver disease or those with a history of ILD, as the drug can exacerbate these conditions.

Gefitinib can interact with other medications, potentially affecting its efficacy and safety profile. Drugs that induce or inhibit cytochrome P450 enzymes, particularly CYP3A4, can alter the metabolism of Gefitinib. For example, CYP3A4 inducers like rifampicin, phenytoin, and St. John’s Wort can decrease plasma concentrations of Gefitinib, reducing its effectiveness. Conversely, CYP3A4 inhibitors such as ketoconazole and erythromycin can increase Gefitinib levels, raising the risk of adverse effects.

Additionally, antacids, H2-receptor antagonists, and proton pump inhibitors can affect the absorption of Gefitinib by altering the gastric pH. Patients should inform their healthcare provider about all medications they are taking, including over-the-counter drugs and supplements, to ensure that potential interactions are appropriately managed.

In conclusion, Gefitinib represents a significant advancement in the treatment of NSCLC, particularly for patients with specific EGFR mutations. Its targeted mechanism of action, combined with ongoing research, continues to improve outcomes for many cancer patients. However, careful monitoring for side effects and potential drug interactions is essential to optimize its therapeutic benefits while minimizing risks. As research progresses, the role of Gefitinib in cancer therapy may expand, offering hope to even more patients in the future.