regorafenib

Regorafenib is an oral multikinase inhibitor used in the treatment of certain advanced cancers. It acts by blocking multiple kinases involved in tumor angiogenesis, oncogenesis, and the tumor microenvironment, thereby reducing blood vessel formation and slowing tumor growth.

The drug targets a broad range of kinases, including VEGF receptors (VEGFR1-3), TIE2, RAF kinases (including wild-type and mutant B-Raf), RET, KIT, and others. It is metabolized in the liver to active metabolites that contribute to its anti-tumor activity. Due to its multi-targeted mechanism, regorafenib can affect several pathways involved in tumor progression and metastasis.

In the United States, regorafenib is approved for metastatic colorectal cancer after progression on standard therapies. It is also approved in various regions for unresectable hepatocellular carcinoma and for unresectable gastrointestinal stromal tumors (GIST). These indications reflect its activity across different tumor types where angiogenesis and signaling pathways play key roles.

Regorafenib is administered orally at 160 mg once daily for 21 days of a 28-day cycle. It should be taken with a meal, preferably a low-fat meal. Dosing may be adjusted or interrupted based on toxicity. Common adverse effects include hypertension, hand–foot syndrome, fatigue, diarrhea, mucositis, weight loss, and elevated liver enzymes. Serious risks include hepatotoxicity, bleeding, thromboembolism, wound-healing impairment, and other gastrointestinal or hematologic events. Patients require regular monitoring of blood pressure, liver function tests, and signs of hemorrhage or infection. Caution is advised with concomitant medications that strongly inhibit or induce CYP3A4, as regorafenib is metabolized in part by hepatic enzymes. Pregnancy should be avoided due to potential fetal harm.