VEGF Flashcards
Avastin (bevicizumab)
Cleared:?
MOA:humanized monoclonal antibody directed against the vascular endothelial growth factor (VEGF). Binds to all isoforms of
VEGF-A.inhibits vessel formation &permeability.
DOSE:15mg/kg.
Notes:wait 1month form surg. Hold for >2gm proteinuria/day
Toxicity 1:GI perforations and wound healing complications.
Toxicity 2:Bleeding complications with epistaxis being most commonly observed. Serious life-threatening pulmonary hemorrhage occur in rare cases in patients with non–small cell lung cancer as outlined previously in Special Considerations.
Toxicity 3:Increased risk of arterial thromboembolic events, including myocardial infarction, angina, and stroke. There is also an increased incidence of venous thromboembolic events.
Toxicity 4:Hypertension occurs in up to 20%–30% of patients with grade 3 hypertension observed in 10%–15% of patients. Usually well controlled with oral antihypertensive medication.
Toxicity 5:Proteinuria with nephrotic syndrome in up to 5% of patients.
Toxicity 6:Infusion-related symptoms with fever, chills, urticaria, flushing, fatigue,
headache, bronchospasm, dyspnea, angioedema, and hypotension. Relatively uncommon (,5%).
Toxicity 7:CNS events with dizziness and depression. RPLS occurs rarely (,0.1%) and presents with headache, seizure, lethargy, confusion, blindness, and other visual disturbances.
Sorafenib
Clearance: hepatic -80%.
Inhibits multiple receptor tyrosine kinases (RTKs), some of which are involved in tumor growth, tumor angiogenesis, and metastasis.
• Potent inhibitor of intracellular kinases, including c-Raf and wildtype and mutant B-Raf.
• Targets vascular endothelial growth factor receptors, VEGF-R2 and VEGF-R3, and platelet-derived growth factor receptor-b (PDGFR-b), and in so doing, inhibits angiogenesis.
Toxicity 1 Hypertension occurs in nearly 30% of patients. Usually occurs within 6 weeks of starting therapy and well-controlled with oral antihypertensive medication.
Toxicity 2 Skin rash occurs in up to 60–70% of patients. Hand–foot skin reaction occurs in up to 30%. Rare cases of actinic keratoses and cutaneous squamous cell cancer have been reported.
Toxicity 3 Bleeding complications with epistaxis most commonly observed.
Toxicity 4 Wound healing complications.
Toxicity 5 Constitutional side effects with fatigue and asthenia.
Toxicity 6 Diarrhea and nausea are the most common GI side effects.
Toxicity 7 Hypophosphatemia occurs in up to 45% of patients, but usually clinically
asymptomatic.
Sunitinib
MOA-signal transduction inhibitor
• Inhibits multiple RTKs, some of which are involved in tumor
growth, tumor angiogenesis, and metastasis.
• Potent inhibitor of platelet-derived growth factor receptors (PDGFR-a and PDGFR-b), vascular endothelial growth factor receptors (VEGF-R1, VEGF-R2, and VEGF-R3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colonystimulating factor receptor type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptors (RET).
Clearance: hepatic
Toxicity 1 Hypertension occurs in up to nearly 30% of patients. Usually occurs within 3–4 weeks of starting therapy and well-controlled with oral anti-hypertensive medication.
Toxicity 2 Yellowish discoloration ofthe skin occursin approximately 30% of patients. Skin rash, dryness, thickness, and/or cracking of skin. Depigmentation of hair and/or skin may also occur.
Toxicity 3 Bleeding complications with epistaxis most commonly observed.
Toxicity 4 Constitutional side effects with fatigue and asthenia, which may be significant in some patients.
Toxicity 5 Diarrhea, stomatitis, altered taste, and abdominal pain are the most common GI side effects. Pancreatitis has been reported rarely with elevations in serum lipase and amylase.
Toxicity 6 Myelosuppression with neutropenia and thrombocytopenia.
Toxicity 7 Increased risk of left ventricular dysfunction, which in some cases results
in CHF.
Toxicity 8 Adrenal insufficiency and hypothyroidism.
Pazopanib
MOA:Oral multikinase inhibitor of angiogenesis.
• Inhibits vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-a and PDGFR–b, fibroblast growth factor receptor (FGFR)-1 and FGFR-3, c-Kit, interleukin-2 receptor inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms).
Clearance:hepatic
Notes:watch LFTs, urine protein and QT prolongation
Toxicity 1 Hypertension occurs in nearly 50% of patients. Usually occurs within the
first 18 weeks of therapy and is well controlled with oral antihypertensive medications. Toxicity 2 Diarrhea, nausea/vomiting, and abdominal pain are the most common
GI side effects. Elevations in serum lipase have been observed in up to 30%
of patients. Increased risk of GI fistulas and/or perforations
Toxicity 3 Fatigue, asthenia, and anorexia may be significant in some patients.
Toxicity 4 Hair color changes with depigmentation.
Toxicity 5 Bleeding complications with hematuria, epistaxis, and hemoptysis.
Toxicity 6 Increased risk of arterial thrombolic events, including myocardial infarc-
tion, angina, TIA, and stroke.
Toxicity 7 Proteinuria develops in 8% of patients.
Toxicity 8 Myelosuppression with neutropenia and thrombocytopenia. Usually mild
to moderate in severity.
Toxicity 9 Hypothyroidism.
Toxicity 10 Elevations in serum transaminases usually observed within the first 18 weeks of therapy. Indirect hyperbilirubinemia may occur in patients with underlying Gilbert’s syndrome.
Toxicity 11 Cardiac toxicity with QT prolongation (≥500 msec) and Torsade de Pointes.
Toxicity 12 Electrolyte abnormalities with hyperglycemia, hypophosphatemia, hypo-
natremia, hypomagnesemia, and hypoglycemia
Everolimus
MOA: Potent inhibitor of the mammalian target of rapamycin (mTOR), a serine-threonine kinase that is a key component of cellular signaling pathways involved in the growth and proliferation of tumor cells.
• Inhibitor of expression of hypoxia-inducible factor (HIF-1), whichleads to reduced expression of VEGF.
• Inhibition of mTOR signaling results in cell cycle arrest, induction ofapoptosis, and inhibition of angiogenesis.
Clearance:hepatic
Toxicity 1: Asthenia and fatigue.
Toxicity 2: Mucositis, oral ulcerations, and diarrhea.
Toxicity 3: Nausea/vomiting and anorexia.
Toxicity 4:Increased risk of opportunistic infections, such as pneumonia, other bacterial infections, and invasive fungal infections.
Toxicity 5: Pulmonary toxicity in the form of increased cough, dyspnea, fever, and pulmonary infiltrates.
Toxicity 6: Skin rash.
Toxicity 7: Myelosuppression with anemia, thrombocytopenia, and neutropenia.
Toxicity 8: Hyperlipidemia with increased serum triglycerides and/or cholesterol in up to 70–75% of patients.
Toxicity 9:Hyperglycemia in up to 50% of patients.
Toxicity 10: Mild liver toxicity with elevation in serum transaminases and alkaline phosphatase.
