Introduction
Cabozantinib is a multi-target tyrosine kinase inhibitor used in the treatment of several advanced cancers, including medullary thyroid cancer, advanced renal cell carcinoma, and hepatocellular carcinoma. It works by inhibiting multiple receptor tyrosine kinases involved in tumor growth, angiogenesis, and metastasis.
Uses
Cabozantinib is a tyrosine kinase inhibitor used to treat advanced renal cell carcinoma, hepatocellular carcinoma, and medullary thyroid cancer.
Cabozantinib is indicated for the treatment of progressive, metastatic medullary thyroid cancer. It is also indicated for the treatment of advanced renal cell carcinoma and for hepatocellular carcinoma in patients previously treated with sorafenib.
Associated Conditions
Pharmacodynamics
Cabozantinib suppresses metastasis, angiogenesis, and oncognesis by inhibiting receptor tyrosine kinases.
Mechanism of Action
Cabozantinib inhibits specific receptor tyrosine kinases such as VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, RET, MET, and TIE-2.
Absorption
After oral administration, peak plasma concentration was achieved in 2-5 hours.
Volume of Distribution
The volume of distribution is 349L.
Protein Binding
Cabozantinib has extensive plasma protein binding (≥ 99.7%).
Route of Elimination
Cabozantinib is eliminated mostly by the feces (54%) and also by the urine (27%).
Half Life
Cabozantinib has a long half-life of 55 hours.
Clearance
At steady state, the clearance is 4.4 L/hr.
Toxicity
Cabozantinib carries a warning of serious gastrointestinal fistulas and perforations, and potentially fatal hemoptysis and gastrointestinal hemorrhage.
Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase levels of cabozantinib.
- Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of cabozantinib.
- Take on an empty stomach. Separate the administration of cabozantinib from food by at least 1 hour before or 2 hours after eating.
- Take with a full glass of water.
Dosage
Recommended Dosage for Hepatocellular Carcinoma: The recommended dosage of Cabozantinib is 60 mg once daily without food until disease progression or unacceptable toxicity. Or, as directed by the registered physicians.
- Stop treatment with Cabozantinib at least 28 days prior to scheduled surgery, including dental surgery.
- Do not substitute Cabozantinib tablets with Cabozantinib capsules.
- Do not administer Cabozantinib with food. Administer at least 1 hour before or at least 2 hours after eating.
- Swallow Cabozantinib tablets whole. Do not crush Cabozantinib tablets.
- Do not take a missed dose within 12 hours of the next dose.
- Modify the dose for certain patients with hepatic impairment and for patients taking drugs known to strongly induce or inhibit CYP450.
