II. Indications
-
Renal Cell Cancer (advanced)
- Axitinib
- Cabozantinib (Cometrig)
- Lenvatinib (Lenvima)
- Sunitinib (Sutent)
- Sorafenib (Nexavar)
-
Medullary Thyroid Cancer (metastatic)
- Cabozantinib (Cometrig)
- Differentiated Thyroid Cancer (refractory)
- Lenvatinib (Lenvima)
- Sorafenib (Nexavar)
-
Hepatocellular Carcinoma (unresectable)
- Cabozantinib (Cometrig)
- Lenvatinib (Lenvima)
- Regorafenib
- Sorafenib (Nexavar)
-
Colorectal Cancer (metastatic)
- Regorafenib
- Gastrointestinal stromal tumors
- Regorafenib
- Sunitinib (Sutent)
- Pancreatic Neuroendocrine Tumor
- Sunitinib (Sutent)
III. Mechanism
-
Vascular Endothelial Growth Factor Receptor (VEGF, VEGFR)
- Angiogenesis signaling Protein
- Binds to VEGF receptors on Tyrosine Kinases to initiate Angiogenesis
- Target in some Targeted Cancer Therapy (e.g. Avastin)
- Other functions
- Monocyte activation and differentiation (VEGFR 1)
- Also used in Age-Related Macular Degeneration as a VEGF Inhibitor Intravitreal Injection
- Angiogenesis signaling Protein
- VEGFR Inhibitors
- Broad group of small molecule inhibitors of VEGFR (specifically VEGFR2 with or without VEGFR 1 and/or 3)
- Most VEGFR blocking agents, also block multiple other Tyrosine Kinases
IV. Medications
- Axitinib (Inlyta)
- Oral small molecule agent inhibits proangiogenic Cytokines (VEGFR, PDGFR)
- Risk of Severe Hypertension including PRES, thrombosis, bleeding, GI perforation, Hypothyroidism, hepatotoxicity
- Avoid with strong CYP3A4/5 Inhibitors and Inducers
- Cabozantinib (Cometrig)
- Oral agent blocks multiple small molecule receptor Tyrosine Kinases affecting tumor growth and Angiogenesis
- In addition to VEGFR 1-3, blocks MET, RET, KIT, FLT-3, TIE-2, TRKB and AXL
- Risk of Severe Hypertension, thrombosis, bleeding, GI perforation, Diarrhea, hepatotoxicity, palmar-plantar erythrodysesthesia
- Lenvatinib (Lenvima)
- Oral small molecule agent blocking VEGFR2
- Risk of Hypertension, arterial thrombosis, bleeding, GI perforation, Prolonged QT, hepatotoxicity, Renal Failure, Hypocalcemia, Cardiomyopathy
- Pazopanib (Votrient)
- Oral small molecule agent blocks VEGFR 1-3, c-Kit, and PDGF-R
- Risk of arterial thrombosis, bleeding, Prolonged QT, hepatotoxicity, Retinal Detachment, polycythemia, Interstitial Lung Disease
- Avoid with Antacids (decreased absorption)
-
Ponatinib (Iclusig)
- Oral small molecule agent blocks VEGFR, as well as BCR-ABL (see BCR-ABL Inhibitor), FGFR, FLT3 and TIE2
- Ponatinib inhibits both unmutated and mutated forms of Bcr-Abl, including highly drug resistant mutations
- Ponatinib is associated with serious cardiovascular events (CVA, MI, PVD) in 20-30%, mortality in 1% (black box warning)
- Ponatinib also has a black box warning for hepatotoxicity
- Regorafenib (Stivarga)
- Oral small molecule agent blocks VEGFR 2-3, as well as Ret, c-Kit, PDGFR and Raf kinases
- Risk of hepatotoxicity (black box)
- Does not require dose adjustments in hepatic Impairment (mild-moderate) or renal Impairment (moderate-severe)
- Avoid with strong CYP3A4 Inhibitors and Inducers
- Sunitinib (Sutent)
- Oral small molecule agent blocks VEGFR2 and PDGFRb, as well as c-kit and FLT3
- Risk of hepatotoxicity, Prolonged QT, bleeding, Cardiomyopathy, adrenal toxicity, GI Perforation, myelosuppression, Hypertension, Thyroid dysfunction
- Also may cause Tumor Lysis Syndrome
- Sorafenib (Nexavar)
- Oral small molecule agent blocks VEGFR2 and PDGFRb, as well as RAF
- Risk of bleeding, Cardiomyopathy, GI perforation, hepatotoxicity, severe rash (SJ/TEN), Hypertension
- Take 1 hour before or 2 hours after a meal (best absorption)
- Vandetanib (Capreisa)
- Oral small molecule agent blocks VEGFR2, as well as EGFR
- Risk of GI perforation, Prolonged QT (black box), Interstitial Lung Disease, impaired Wound Healing
- Also risk of Hypertension, CVA, Cardiomyopathy, severe rash (SJ/TEN)
-
Ziv-Aflibercept (Zaltrap)
- Ziv-Aflibercept has a unique mechanism of VEGF Inhibitors
- Recombinant fusion Protein that acts as a decoy for Vascular Endothelial Growth Factor (VEGF) receptors
V. Dosing
- See other references for disease specific dosing protocols
VI. Adverse Effects
- Cardiovascular
- Severe Hypertension including PRES (Axitinib, Cabozantinib, Lenvatinib, Sorafenib, Vandetanib)
- Venous Thromboembolism (Axitinib, Cabozantinib)
- Arterial occlusive events (Axitinib, Cabozantinib,Lenvatinib, Pazopanib, and ACS with Sorafenib, CVA with Vandetanib)
- Cardiomyopathy or cardiac failure (Lenvatinib, Sunitinib, Vandetanib)
- Prolonged QTc (Lenvatinib, Pazopanib, Sunitinib, Vandetanib)
- Pulmonary
- Interstitial Lung Disease (Pazopanib, Vandetanib)
- Hematologic
- Bleeding risk and Hemorrhage (Axitinib, Cabozantinib, Lenvatinib, Sunitinib, Sorafenib)
- Polycythemia (Pazopanib)
- Neutropenia (Pazopanib with east asian descent)
- Thrombocytopenia (Pazopanib with east asian descent)
- Tumor Lysis Syndrome (Sunitinib)
- Endocrine
- Adrenal Toxicity (Sunitinib)
- Hypothyroidism (Axitinib, Sunitinib)
- Hypocalcemia (Lenvatinib)
- Eye
- Retinal Detachment (Pazopanib)
- Dermatologic
- Palmar-plantar erythrodysesthesia or PPES (Cabozantinib, Pazopanib with east asian descent)
- Hair or skin depigmentation (Sunitinib)
- Yellow Skin Discoloration (Sunitinib)
- Impaired Wound Healing (Axitinib, Vandetanib)
- Severe dermatologic reaction (Vandetanib, Sorafenib)
- Steven Johnson Syndrome (SJS)
- Toxic Epidermal Necrolysis (TEN)
- Gastrointestinal
- Gastrointestinal perforation (Axitinib, Cabozantinib, Lenvatinib, Sunitinib, Sorafenib, Vandetanib)
- Hepatotoxicity (Axitinib, Cabozantinib, Pazopanib, Regorafenib, Sunitinib, Sorafenib)
- Severe Diarrhea (Cabozantinib)
- Renal
- Proteinuria (Axitinib, Cabozantinib, Lenvatinib)
- Acute Renal Failure (Cabozantinib)
VII. Safety
- Avoid in Lactation
- Avoid in pregnancy (all trimesters, pregnancy category X)
- Use reliable Contraception
- Continue Contraception for at least 4 months after Vandetanib
- Monitoring
- Complete Blood Count
- Liver Function Tests (Cabozantinib)
- Electrocardiogram for Prolonged QT (Lenvatinib, Pazopanib, Sunitinib, Vandetanib)
- INR (Sunitinib, Sorafenib)
- Blood Pressure (Axitinib, Cabozantinib, Lenvatinib, Sorafenib)
VIII. Drug Interactions
- Strong CYP3A4/5 Inhibitors and Inducers
- Avoid with Axitinib, Regorafenib
- Avoid strong CYP3A4 inducers with Vandetanib
- Increased Sunitinib levels with inihibitors, decreased levels with inducers
-
Antacids
- Avoid with Pazopanib
-
Medication Causes of QTc Prolongation
- Avoid with Lenvatinib, Pazopanib, Sunitinib
- BCRP Substrates
- Regorafenib may increase levels
- INR
- Increased with Sunitinib, Sorafenib
IX. Resources
- Axitinib (DailyMed)
- Cabozantinib (DailyMed)
- Lenvatinib (DailyMed)
- Pazopanib (DailyMed)
- Ponatinib (DailyMed)
- Regorafenib (DailyMed)
- Sunitinib (DailyMed)
- Sorafenib (DailyMed)
- Vandetanib (DailyMed)
Images: Related links to external sites (from Bing)
Related Studies
sutent (on 1/1/2023 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
SUTENT 12.5 MG CAPSULE | $215.93 each | |
SUTENT 25 MG CAPSULE | $435.98 each |
Ontology: sunitinib (C1176020)
Definition (NCI_NCI-GLOSS) | A drug used to treat gastrointestinal stromal tumors (GIST) that have not responded to treatment with imatinib mesylate (Gleevec). Sunitinib is also used to treat advanced kidney cancer and is being studied in the treatment of other types of cancer. It is a type of tyrosine kinase inhibitor, a type of vascular endothelial growth factor (VEGF) receptor inhibitor, and a type of angiogenesis inhibitor. |
Definition (NCI) | An indolinone derivative and tyrosine kinase inhibitor with potential antineoplastic activity. Sunitinib blocks the tyrosine kinase activities of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor b (PDGFRb), and c-kit, thereby inhibiting angiogenesis and cell proliferation. This agent also inhibits the phosphorylation of Fms-related tyrosine kinase 3 (FLT3), another receptor tyrosine kinase expressed by some leukemic cells. |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C473478 |
SnomedCT | 421192001, 421448007 |
English | 5-(5-fluoro-2-oxo-1,2-dihydroindolylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, Sunitinib, Sunitinib (product), Sunitinib (substance), sunitinib, sunitinib (medication), 1H-Pyrrole-3-carboxamide, N-(2-(diethylamino)ethyl)-5-((Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2,4-dimethyl-, sunitinib [Chemical/Ingredient], SUNItinib, SUNITINIB |
Spanish | sunitinib (sustancia), sunitinib, sunitinib (producto) |
Ontology: sorafenib (C1516119)
Definition (NCI_NCI-GLOSS) | A drug used to treat advanced kidney cancer and a type of liver cancer that cannot be removed by surgery. It is also being studied in the treatment of other types of cancer. Sorafenib stops cells from dividing and may prevent the growth of new blood vessels that tumors need to grow. It is a type of kinase inhibitor and a type of antiangiogenesis agent. |
Definition (NCI) | A synthetic compound targeting growth signaling and angiogenesis. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway that controls cell division and proliferation; in addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, thereby blocking tumor angiogenesis. |
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
MSH | C471405 |
SnomedCT | 420681006, 422042001 |
LNC | LP172583-9, MTHU046381 |
English | Sorafenib, Sorafenib (product), Sorafenib (substance), sorafenib (medication), SORAFENIB, sorafenib [Chemical/Ingredient], SORAfenib, SFN, sorafenib, 4-(4-(3-(4-chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxyllic acid methyamide-4-methylbenzenesulfonate |
Spanish | sorafenib (sustancia), sorafenib, sorafenib (producto) |
Ontology: Vandetanib (C1628324)
Definition (NCI_NCI-GLOSS) | A substance being studied in the treatment of lung cancer and other types of cancer. It may block the growth and spread of tumor cells and prevent the growth of new blood vessels that tumors need to grow. Vandetanib is a type of tyrosine kinase inhibitor and a type of antiangiogenesis agent. |
Definition (NCI) | An orally bioavailable 4-anilinoquinazoline. Vandetanib selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2), thereby blocking VEGF-stimulated endothelial cell proliferation and migration and reducing tumor vessel permeability. This agent also blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that mediates tumor cell proliferation and migration and angiogenesis. |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C452423 |
SnomedCT | 418520004, 418260004 |
Spanish | vandetanib (producto), vandetanib (sustancia), vandetanib |
English | vandetanib, Vandetanib, VANDETANIB, Vandetanib (product), Vandetanib (substance) |
Japanese | バンデタニブ |
Ontology: axitinib (C1700874)
Definition (NCI) | An orally bioavailable tyrosine kinase inhibitor. Axitinib inhibits the proangiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor (PDGF), thereby exerting an anti-angiogenic effect. |
Definition (NCI_NCI-GLOSS) | A substance that is being studied in the treatment of cancer. It belongs to the families of drugs called angiogenesis inhibitors and protein tyrosine kinase inhibitors. |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C503983 |
SnomedCT | 427882000, 429507005 |
English | axitinib, Axitinib (substance), Axitinib (product), Axitinib, N-methyl-2-((3-((1E)-2-(pyridin-2-yl)ethenyl)-1H-indazol-6-yl)sulfanyl)benzamide, chemotherapeutics growth-signaling inhibitors axitinib, chemotherapeutics growth-signaling inhibitors axitinib (medication), AXITINIB |
Spanish | Axitinib, axitinib (producto), axitinib, Axitinib (sustancia) |
Ontology: pazopanib (C1831796)
Definition (NCI_NCI-GLOSS) | A drug that is used to treat kidney cancer and is being studied in the treatment of other types of cancer. It may prevent the growth of new blood vessels that tumors need to grow. It is a type of protein tyrosine kinase inhibitor and a type of antiangiogenesis agent. |
Definition (NCI) | A small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R), which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated. |
Definition (PDQ) | A novel small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R), which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=476479&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=476479&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C60779" NCI Thesaurus) |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C516667 |
SnomedCT | 443763005, 443764004 |
English | pazopanib, Pazopanib (substance), Pazopanib, Pazopanib (product), Benzenesulfonamide, 5-((4-((2,3-dimethyl-2H-indazol-6-yl)methylamino)-2-pyrimidinyl)amino)-2-methyl-, PAZOPANIB |
Spanish | pazopanib (sustancia), pazopanib, pazopanib (producto) |
Ontology: Vascular Endothelial Growth Factor Receptor Inhibitors [MoA] (C2267120)
Concepts | Molecular Function (T044) |
English | Vascular Endothelial Growth Factor Receptor Inhibitors, Vascular Endothelial Growth Factor Inhibitor, Vascular Endothelial Growth Factor Receptor Inhibitors [MoA] |
Ontology: regorafenib (C2980094)
Definition (NCI) | An orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis; the receptor tyrosine kinases RET, KIT, and PDGFR, and the serine/threonine-specific Raf kinase are involved in tumor cell signaling. |
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
MSH | C559147 |
SnomedCT | 703808002, 702804006 |
English | 4-(4-(((4-chloro-3-(trifluoromethyl)phenyl)carbamoyl)amino)-3-fluorophenoxy)-N-methylpyridine-2-carboxamide, REGORAFENIB, regorafenib, 4-(4-(((4-chloro-3-(trifluoromethyl)phenyl)carbamoyl)amino)-3-fluorophenoxy)-n-methylpyridine-2-carboxamide, regorafenib (medication), chemotherapeutics regorafenib, Regorafenib (product), Regorafenib, Regorafenib (substance) |
Ontology: Lenvatinib Mesylate (C2987642)
Definition (NCI) | 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. |
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
English | Lenvatinib Mesylate, Multi-Kinase Inhibitor E7080, 6-Quinolinecarboxamide, 4-[3-chloro-4-[[(cyclopropylamino)carbonyl]amino]phenoxy]- 7-methoxy-, methanesulfonate (1:1), LENVATINIB MESYLATE |
Ontology: cabozantinib (C3181682)
Definition (NCI) | An orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Cabozantinib strongly binds to and inhibits several RTKs, which are often overexpressed in a variety of cancer cell types, including hepatocyte growth factor receptor (MET), RET (rearranged during transfection), vascular endothelial growth factor receptor types 1 (VEGFR-1), 2 (VEGFR-2), and 3 (VEGFR-3), mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (FLT-3), TIE-2 (TEK tyrosine kinase, endothelial), tropomyosin-related kinase B (TRKB) and AXL. This may result in an inhibition of both tumor growth and angiogenesis, and eventually lead to tumor regression. |
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
MSH | C558660 |
English | cabozantinib, Cabozantinib, 1,1-Cyclopropanedicarboxamide, N'-[4-[(6,7-dimethoxy-4-quinolinyl)oxy]phenyl]-N-(4- fluorophenyl)-, N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1- dicarboxamide, CABOZANTINIB, cabozantinib (medication), chemotherapeutics cabozantinib |