Regonat is a brand which contains Regorafenib, which is an oral multi-kinase inhibitor. It targets angiogenic, stromal, and oncogenic receptor tyrosine kinases, exhibiting anti-angiogenic activity through dual inhibition of VEGFR2-TIE2 tyrosine kinases.

Mechanism of Action

Regorafenib functions by blocking proteins that signal cancer cells to divide and by inhibiting proteins that promote the growth of new blood vessels necessary for tumor development. This dual action impedes cancer cell proliferation and metastasis.

Indications

• Metastatic Colorectal Cancer (CRC): For patients previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild-type, an anti-EGFR therapy. 

• Advanced Gastrointestinal Stromal Tumors (GIST): For patients who have been previously treated with imatinib mesylate and sunitinib malate.

• Advanced Hepatocellular Carcinoma (HCC): For patients who have been previously treated with sorafenib.

Regonat is a significant therapeutic option for certain advanced cancers, offering a mechanism that targets multiple pathways involved in tumor growth and progression. However, its use requires careful consideration of potential side effects and patient-specific factors to ensure optimal outcomes.

Dosage and Administration

The recommended dose of Regorafenib is 160 mg (four 40 mg tablets) taken orally once daily after a low-fat meal for the first 21 days of each 28-day cycle.

Side Effects

Common side effects include weakness or fatigue, loss of appetite, hand-foot syndrome (palmar-plantar erythrodysesthesia), diarrhea, mouth sores (mucositis), weight loss, infection, high blood pressure, and changes in voice volume or quality (dysphonia). Serious side effects can include liver damage, severe bleeding, blistering and peeling of skin, very high blood pressure requiring emergency treatment, heart attacks, and perforations (holes) in the intestines.

Warnings and Precautions

Regorafenib carries a boxed warning for severe and fatal liver toxicity. It can also cause fetal harm when administered to a pregnant woman, being embryolethal and teratogenic in animal studies at exposures lower than human exposures at the recommended dose. Patients should be advised of these risks.

Pharmacokinetics

Regorafenib reaches peak plasma levels approximately 3 to 4 hours after a single oral dose. A high-fat meal decreases its absorption, while a low-fat meal may increase it compared to fasting conditions. The drug is mainly metabolized in the liver by oxidative metabolism via CYP3A4 and glucuronidation by UGT1A9. Its half-life ranges from 20 to 30 hours, and it is primarily excreted in feces (71%) and urine (19%).