Crizotinib
Overview
Crizotinib is an oral targeted anticancer medicine used primarily for the treatment of specific types of non-small cell lung cancer. It works by selectively inhibiting the activity of abnormal ALK, known as anaplastic lymphoma kinase, and ROS1 gene rearrangements that cause uncontrolled cancer cell growth. By blocking these kinases, crizotinib helps to slow or stop tumor progression in patients whose cancers carry these genetic alterations. The medicine is taken orally in capsule form and is generally well tolerated compared to conventional chemotherapy. It has become a first-line treatment option for advanced ALK-positive non-small cell lung cancer and also plays a key role in the management of ROS1-positive tumors.
Background and Date of Approval
Crizotinib was developed by Pfizer and received its first approval from the United States Food and Drug Administration in August 2011 for the treatment of ALK-positive metastatic non-small cell lung cancer. Subsequent approvals were granted by the European Medicines Agency and the Drugs Controller General of India. The pivotal PROFILE 1001 and PROFILE 1007 clinical trials demonstrated that patients treated with crizotinib experienced significant tumor shrinkage and improved progression-free survival compared with chemotherapy. Crizotinib acts as a multitargeted tyrosine kinase inhibitor that blocks ALK, ROS1, and MET kinases. Its approval marked a major advance in personalized oncology, as it established genetic testing for ALK and ROS1 mutations as a standard diagnostic step in lung cancer management.
Uses
Crizotinib is indicated for the treatment of adults with advanced or metastatic non-small cell lung cancer whose tumors are ALK-positive or ROS1-positive. It may also be used in certain rare tumors such as inflammatory myofibroblastic tumors that carry ALK rearrangements. The medicine is prescribed only after confirmation of ALK or ROS1 positivity through validated molecular testing. Crizotinib is typically used as monotherapy, as it works effectively on its own in genetically defined patient groups and does not usually require combination with other anticancer agents.
Administration
Crizotinib is taken orally, usually as a capsule. The standard adult dosage is 250 milligrams twice daily, about twelve hours apart, with or without food. Treatment continues until the disease progresses or the patient develops unacceptable toxicity. Dose adjustments may be needed in individuals with liver or kidney impairment or those who experience side effects such as visual disturbances or heart rhythm changes. The capsules should be swallowed whole and not opened or crushed. Regular monitoring of liver function, vision, and heart rhythm is recommended throughout treatment.
Side Effects
The most commonly reported side effects of crizotinib include nausea, vomiting, diarrhea, constipation, fatigue, visual disturbances such as blurred vision or light trails, and fluid retention. Other effects may include dizziness, altered taste sensation, and mild elevations in liver enzymes. Most side effects are mild to moderate and can often be managed with supportive care or by adjusting the dosage as advised by the healthcare provider.
Warnings
Serious adverse reactions may include liver toxicity, interstitial lung disease or pneumonitis, prolongation of the QT interval on the electrocardiogram, and slow heart rate. Liver function tests should be done before starting treatment and monitored regularly during therapy. Crizotinib should be used cautiously in patients with preexisting heart problems or those taking other medicines that can prolong the QT interval. Rare but serious cases of vision loss and severe lung toxicity have been reported. If life-threatening toxicity occurs, the medicine should be discontinued permanently.
Precautions
Crizotinib is primarily metabolized by the enzyme CYP3A4, so drugs that strongly inhibit or induce this enzyme can alter its levels in the body. Medicines such as ketoconazole, rifampicin, and certain anticonvulsants may increase or decrease crizotinib concentrations and should be avoided when possible. Care is needed when using crizotinib with anticoagulants, blood pressure medicines, or other drugs that affect heart rhythm. It is not recommended for use during pregnancy or breastfeeding, as it may cause harm to the fetus. Patients are advised to avoid consuming grapefruit or grapefruit juice while on therapy.
Expert Tips
Before starting treatment, it is important to confirm ALK or ROS1 positivity through validated molecular testing. Periodic monitoring of liver enzymes and heart function is recommended during therapy. Patients should be counseled to report any new respiratory symptoms or changes in vision immediately. Adherence to the prescribed twice-daily dosing schedule is essential for optimal results. The medicine should be stored at room temperature in a dry place and kept out of reach of children.