Regorafenib is a kinase inhibitor that is indicated:
For the treatment of metastatic colorectal cancer (CRC) after disease progression on or intolerance to fluoropyrimidine-based chemotherapy, anti-VEGF therapy and anti-EGFR therapy.
For the treatment of unresectable or metastatic gastrointestinal stromal tumours (GIST) after disease progression on or intolerance to prior treatment with imatinib and sunitinib. ... Read moreRegorafenib is a kinase inhibitor that is indicated:
For the treatment of metastatic colorectal cancer (CRC) after disease progression on or intolerance to fluoropyrimidine-based chemotherapy, anti-VEGF therapy and anti-EGFR therapy.
For the treatment of unresectable or metastatic gastrointestinal stromal tumours (GIST) after disease progression on or intolerance to prior treatment with imatinib and sunitinib.
For the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib
Targeted Cancer Therapy
Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, metastasis and tumor immunity. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAF V600E, SAPK2, PTK5, Abl and CSF1R at concentrations of regorafenib that have been achieved clinically. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model and inhibition of tumor growth in several mouse xenograft models including some for human colorectal carcinoma, gastrointestinal stromal and hepatocellular carcinoma. Regorafenib also demonstrated anti-metastatic activity in a mouse xenograft model and two mouse orthotopic models of human colorectal carcinoma.
CYP3A4 Inhibitors: Avoid concomitant use of strong CYP3A4 inhibitors with Regorafenib.CYP3A4 Inducers: Avoid concomitant use of strong CYP3A4 inducers with Regorafenib.
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The most common side effects (≥30%) are asthenia/fatigue, decreased appetite and food intake, hand-foot skin reaction (HFSR) [palmar-plantar erythrodysesthesia (PPE)], diarrhea, mucositis, weight loss, infection, hypertension, and dysphonia.
Pregnancy: Based on animal studies and its mechanism of action, Regorafenib can cause fetal harm when administered to a pregnant woman. There are no available data on Regorafenib use in pregnant women. Administration of regorafenib was embryolethal and teratogenic in rats and rabbits at exposures lower than human exposures at the recommended dose, with increased incidences of cardiovascular, genitourinary, and skeletal malformations. Advise pregnant women of the potential hazard to a fetus.The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 % and 15 to 20%, respectively.Lactation: There are no data on the presence of regorafenib or its metabolites in human milk, the effects of regorafenib on the breastfed infant, or on milk production. In rats, regorafenib and its metabolites are excreted in milk. Because of the potential for serious adverse reactions in breastfed infants from Regorafenib, do not breastfeed during treatment with Regorafenib and for 2 weeks after the final dose.
Hemorrhage: Permanently discontinue regorafenib for severe or life-threatening hemorrhage.
Dermatological toxicity: Interrupt and then reduce or discontinue regorafenib depending on severity and persistence of dermatologic toxicity.
Hypertension: Temporarily or permanently discontinue regorafenib for severe or uncontrolled hypertension.
Cardiac ischemia and infarction: Withhold regorafenib for new or acute cardiac ischemia/infarction and resume only after resolution of acute ischemic events.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue regorafenib.
Gastrointestinal perforation or fistulae: Discontinue regorafenib.
Wound healing complications: Stop regorafenib before surgery. Discontinue in patients with wound dehiscence.
Embryofetal toxicity: Can cause fetal harm. Advise women of potential risk to a fetus.
The highest dose of Regorafenib studied clinically is 220 mg per day. The most frequently observed adverse drug reactions at this dose were dermatological events, dysphonia, diarrhea, mucosal inflammation, dry mouth, decreased appetite, hypertension, and fatigue. There is no known antidote for Regorafenib overdose. In the event of suspected overdose, interrupt Regorafenib, institute supportive care, and observe until clinical stabilization.
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
Targeted Cancer Therapy
Regorafenib is a kinase inhibitor and it inhibits multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment. Regorafenib or its major human active metabolites M-2 and M-5 inhibits the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl. Due to its inhibitory functions, regorafenib can inhibit the progression of certain solid tumors.
Regorafenib is Pregnancy Category D. Based on its mechanism of action, Regorafenib can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies with Regorafenib in pregnant women. Based on animal reproduction studies Regorafenib was seen to cause embryo lethal and teratogenic defects and also increased the incidences of cardiovascular, genitourinary, and skeletal malformations in animals. Advice pregnant women or women with reproductive potential of the potential hazards of Regorafenib to the fetus. There is no information regarding the presence of regorafenib or its metabolites being excreted in human milk. Regorafenib and its metabolites were excreted in rat milk and because of the potential for serious adverse reactions in nursing infants from Regorafenib, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
