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Case History

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Image not available. A 65-year-old patient with metastatic clear-cell carcinoma of the kidney is waiting to be seen in the outpatient clinic. The patient is attending for a drug toxicity review, having started sunitinib three weeks ago.

During treatment the patient has experienced intermittent nose bleeds, indigestion, and soreness to his hands and feet. His wife has noticed a yellow tinge to his skin and swelling of his eyelids. The clinic nurse is concerned by his elevated blood pressure recordings.

What class of drug is sunitinib, and what other angiogenic agents exist in clinical use?

What are the side-effects of inhibiting angiogenesis?

How should this patient be managed with regards to toxicity from antiangiogenic therapy?

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Background

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What class of drug is sunitinib?

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Image not available. Sunitinib, delivered orally, inhibits multiple receptor tyrosine kinases (RTKs) that are involved in angiogenesis, tumour growth and metastatic progression of cancer.1-4 The antiangiogenic effect results from inhibition of vascular endothelial growth factor receptors (VEGFR) VEGFR1, VEGFR2 and VEGFR3.1,2 In addition, sunitinib also inhibits platelet-derived growth factor receptors (PDGFR) PDGFRA and PDGFRB, stem cell growth factor receptor (KIT), fms-related tyrosine kinase 3 (FLT3), colony-stimulating factor 1 receptor (CSF1R), and the glial cell line-derived neurotrophic factor receptor (RET).1,2,4

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Are there other drugs in clinical use that target angiogenesis?

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There are now a number of therapeutic agents available for use in clinical practice that target angiogenesis (the formation of new blood vessels) to slow tumour growth and metastasis. Some of the common drugs are listed in Table 14.1.

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Table 14.1*Drugs targeting angiogenesis
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The angiogenesis-related signalling pathways are important to physiological response and homeostasis in many tissues and organs. They play important roles in haematopoiesis, myelopoiesis, endothelial cell survival, tissue growth and wound healing.1,2 Accordingly, the blockage of these pathways by inhibitors has produced a wide range of toxicities, which are determined by the sites of action of the individual drugs (Table 14.2).

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Table 14.2Side-effects of antiangiogenic drugs

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