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Cabozantinib: Uses, Mechanism & Side Effects

Cabozantinib is a targeted cancer therapy used to treat certain malignant tumors by blocking signals that drive tumor growth and spread.

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Things worth knowing about "Cabozantinib"

Cabozantinib is a targeted cancer therapy used to treat certain malignant tumors by blocking signals that drive tumor growth and spread.

What is Cabozantinib?

Cabozantinib is a tyrosine kinase inhibitor (TKI) belonging to the class of targeted cancer therapies. It works by blocking multiple proteins involved in tumor growth and blood vessel formation. The drug is marketed under the brand names Cabometyx and Cometriq and is taken orally, either as a tablet or capsule.

Indications

Cabozantinib has been approved by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for the following conditions:

Renal cell carcinoma (RCC): as first- or second-line therapy, including in combination with the immunotherapy agent nivolumab
Hepatocellular carcinoma (HCC): liver cancer previously treated with sorafenib
Medullary thyroid cancer (MTC): a rare, aggressive form of thyroid cancer
Differentiated thyroid cancer (DTC): after failure of radioiodine therapy in progressive disease

Mechanism of Action

Cabozantinib simultaneously inhibits multiple receptor tyrosine kinases -- enzymes that transmit signals controlling cell growth and survival. Key targets include:

MET (hepatocyte growth factor receptor): promotes tumor growth and metastasis
VEGFR-1, -2, -3 (vascular endothelial growth factor receptors): regulate the formation of new blood vessels in the tumor (angiogenesis)
RET: frequently mutated in medullary thyroid cancer
AXL and KIT: involved in tumor immunology and resistance mechanisms

By blocking these pathways simultaneously, cabozantinib cuts off the tumor's blood supply, reduces its capacity to spread (metastasize), and promotes cancer cell death (apoptosis).

Dosage and Administration

The dosage depends on the specific indication and the formulation used:

Cabometyx (tablets): typically 60 mg once daily for kidney and liver cancer; 40 mg when combined with nivolumab
Cometriq (capsules): 140 mg daily for medullary thyroid cancer

The medication should be taken on an empty stomach. Grapefruit juice and certain other drugs can alter its effectiveness and should be avoided during treatment.

Side Effects

Like all tyrosine kinase inhibitors, cabozantinib can cause a range of side effects. The most common include:

Diarrhea, nausea, and vomiting
Hand-foot syndrome (redness, pain, and blistering on the palms and soles)
Fatigue and weakness
High blood pressure (hypertension)
Weight loss and decreased appetite
Elevated liver enzyme levels
Impaired wound healing, and rarely fistula formation or gastrointestinal perforation

Serious side effects such as bleeding events, thromboembolic events, or liver toxicity require close medical monitoring and may necessitate dose reductions or discontinuation of treatment.

Important Warnings

Cabozantinib is contraindicated during pregnancy and breastfeeding, as it may harm the unborn child. Women of childbearing potential must use effective contraception during treatment and for at least four months after the last dose. The therapy is always administered under regular oncological supervision.

References

European Medicines Agency (EMA): Cabometyx - Summary of Product Characteristics. Available at: https://www.ema.europa.eu
Choueiri TK et al. - Cabozantinib plus Nivolumab versus Sunitinib in Advanced Renal-Cell Carcinoma. New England Journal of Medicine, 2021; 384:829-840.
Abou-Alfa GK et al. - Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma (CELESTIAL). New England Journal of Medicine, 2018; 379:54-63.

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