- History Of Lenvatinib
- What Is Lenvatinib?
- Lenvatinib Mechanism of action
- What Is Lenvatinib Used For?
- What Side Effects May I Notice When You Use Lenvatinib?
- Lenvatinib Clinical Results(FDA Approval)
- Where should I keep Lenvatinib?
- Related Drugs: Lenvatinib Mesylate(CAS:857890-39-2)
- Where Can We Buy Lenvatinib online?
History Of Lenvatinib
A phase I clinical trial in cancer patients was performed in 2006. A phase III trial treating thyroid cancer patients started in March 2011.
Lenvatinib was granted orphan drug status for treatment of various types of thyroid cancer that do not respond to radioiodine in the US and Japan in 2012 and in Europe in 2013.
In February 2015, the U.S. FDA approved lenvatinib for treatment of progressive, radioiodine refractory differentiated thyroid cancer. In May 2015, European Medicines Agency (EMA) approved the drug for the same indication.
In May 2016, the FDA approved it (in combination with everolimus) for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy.
In August 2018, the FDA approved lenvatinib for the first-line treatment of people with unresectable hepatocellular carcinoma (HCC).
What Is Lenvatinib?
Lenvatinib(CAS:417716-92-8) is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. These receptor tyrosine kinases (RTKs) located in the cell membrane play a central role in the activation of signal transduction pathways involved in the normal regulation of cellular processes, such as cell proliferation, migration, apoptosis and differentiation, and in pathogenic angiogenesis, lymphogenesis, tumour growth and cancer progression. In particular, VEGF has been identified as a crucial regulator of both physiologic and pathologic angiogenesis and increased expression of VEGF is associated with a poor prognosis in many types of cancers.
Lenvatinib is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer. Most patients with thyroid cancer have a very good prognosis with treatment (98% 5 year survival rate) involving surgery and hormone therapy. However, for patients with RAI-refractory thyroid cancer, treatment options are limited and the prognosis is poor, leading to a push for the development of more targeted therapies such as lenvatinib.
Lenvatinib Mechanism of action
Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.
What Is Lenvatinib Used For?
❶ Lenvatinib is used to treat a certain type of thyroid cancer that has returned or that has spread to other parts of the body and cannot be treated with radioactive iodine.
❷ Lenvatinib is also used along with everolimus (Afinitor, Zortress) to treat renal cell carcinoma (RCC, a type of cancer that begins in the kidney) in people who have previously received treatment with another chemotherapy medication.
❸ Lenvatinib is also used to treat hepatocellular carcinoma (HCC; a type of liver cancer) that cannot be treated with surgery.
❹ Lenvatinib is also used along with pembrolizumab (Keytruda) to treat a certain type of cancer of the endometrium (lining of the uterus) that has spread to other parts of the body or worsened during or after treatment with chemotherapy medications or that cannot be treated with surgery or radiation therapy.
❺ Lenvatinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.
What Side Effects May I Notice When You Use Lenvatinib?
Side effects that you should report to your doctor or health care professional as soon as possible:
▪ allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
▪ breathing problems
▪ chest pain or palpitations
▪ feeling faint or lightheaded, falls
▪ high blood pressure
▪ signs and symptoms of bleeding such as bloody or black, tarry stools; red or dark-brown urine; spitting up blood or brown material that looks like coffee grounds; red spots on the skin; unusual bruising or bleeding from the eye, gums, or nose
▪ signs and symptoms of a dangerous change in heartbeat or heart rhythm like chest pain; dizziness; fast or irregular heartbeat; palpitations; feeling faint or lightheaded, falls; breathing problems
▪ signs and symptoms of kidney injury like trouble passing urine or change in the amount of urine
▪ signs and symptoms of liver injury like dark yellow or brown urine; general ill feeling or flu-like symptoms; light-colored stools; loss of appetite; nausea; right upper belly pain; unusually weak or tired; yellowing of the eyes or skin
▪ signs and symptoms of low potassium like muscle cramps or muscle pain; chest pain; dizziness; feeling faint or lightheaded, falls; palpitations; breathing problems; or fast, irregular heartbeat
▪ signs and symptoms of a stroke like changes in vision; confusion; trouble speaking or understanding; severe headaches; sudden numbness or weakness of the face, arm or leg; trouble walking; dizziness; loss of balance or coordination
▪ stomach pain
▪ swelling of the legs or ankles
▪ unusually weak or tired
Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
▪ joint pain
▪ loss of appetite
▪ mouth sores
▪ muscle pain
▪ nausea, vomiting
▪ weight loss
This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Lenvatinib Clinical Results(FDA Approval)
The FDA approval of Lenvatinib was based on a multicenter, randomized, double-blind, placebo-controlled trial in 392 subjects with locally recurrent or metastatic radioactive iodine-refractory differentiated thyroid cancer and radiographic evidence of disease progression within 12 months prior to randomization, confirmed by independent radiologic review. The subjects received Lenvatinib 24 mg once daily (n=261) or placebo (n=131) until disease progression. Study results showed Lenvatinib-treated subjects lived a median of 18.3 months without their disease progressing (progression-free survival), compared to a median of 3.6 months for subjects who received placebo. Additionally, 65% of subjects treated with Lenvatinib saw a reduction in tumor size, compared to 2% of subjects who received a placebo.
Where should I keep Lenvatinib?
Keep out of the reach of children.
Store between 20 and 25 degrees C (68 and 77 degrees F). Throw away any unused medicine after the expiration date.
NOTE: This sheet is a summary. It may not cover all possible information. If you have questions about this medicine, talk to your doctor, pharmacist, or health care provider.
Related Drugs: Lenvatinib Mesylate(CAS:857890-39-2)
Lenvatinib mesylate(CAS:857890-39-2) is a synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. E7080 blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis.
Lenvatinib mesylate is a methanesulfonate salt obtained by reaction of lenvatinib with one molar equivalent of methanesulfonic acid. A multi-kinase inhibitor and orphan drug used (as its mesylate salt) for the treatment of various types of thyroid cancer that do not respond to radioiodine. It has a role as an EC 188.8.131.52 (receptor protein-tyrosine kinase) inhibitor, a fibroblast growth factor receptor antagonist, an orphan drug, a vascular endothelial growth factor receptor antagonist and an antineoplastic agent. It contains a lenvatinib(1+).
Lenvatinib mesylate is approved to be used alone or with other drugs to treat:
♦ Endometrial carcinoma that is advanced and got worse after other therapies. It is used with pembrolizumab in patients whose cancer is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and cannot be treated with surgery or radiation therapy.
♦ Hepatocellular carcinoma (a type of liver cancer). It is used as first-line treatment in patients whose disease cannot be removed by surgery.
♦ Renal cell carcinoma (a type of kidney cancer) that is advanced. It is used with everolimus in patients who have already received angiogenesis inhibitor therapy.
♦ Thyroid cancer in certain patients with progressive, recurrent, or metastatic disease that does not respond to treatment with radioactive iodine.
This use is approved under FDA’s Accelerated Approval Program. As a condition of approval, confirmatory trial(s) must show that lenvatinib mesylate provides a clinical benefit in these patients. Lenvatinib mesylate is also being studied in the treatment of other types of cancer.
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 E. Cabanillas, M. Schlumberger, B. Jarzab, et al.A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: a clinical outcomes and biomarker assessment Cancer, 121 (16) (2015), pp. 2749-2756.