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Case history

image A 65-year-old man with metastatic clear cell carcinoma of the kidney presented to the medical assessment unit. He had undergone a radical nephrectomy 2 years previously for a clear cell carcinoma (pT3apN0M0, Leibovich score 7) and had subsequently developed lung and bone metastases. As his risk had been assessed to be favourable according to the International Metastatic Renal Cell Carcinoma Database Consortium prognostic grouping, following discussion with his oncologist he had opted to commence systemic treatment and had started oral pazopanib therapy 4 weeks earlier.

He presented acutely with symptoms of headache, nausea and diarrhoea. During treatment he had also experienced indigestion, mucositis and fatigue. His wife had noticed a swelling of his eyelids. The clinic nurse was concerned by his elevated blood pressure recordings. He had a history of hypertension that was being treated with a calcium channel blocker.

The patient was reviewed at an oral therapies review clinic with experience in the management of patients with antiangiogenic therapy. As the severity of his symptoms and raised blood pressure were deemed to be a significant risk, pazopanib was interrupted and he was treated with supportive measures including oral care and oral antacids. Two weeks later he restarted treatment at 75% of the standard dose. His blood pressure was monitored daily using a home blood pressure monitor and he was seen at 2 weekly intervals in the clinic, where adjustments to his antihypertensive treatment were made. He was able to tolerate further courses of pazopanib and achieved a good partial response to therapy lasting over a year.

What class of drug does pazopanib belong to and what is the mechanism of action?

Are there others drugs in clinical use that target angiogenesis?

Is hypertension a common side effect?

What are the other potential cardiovascular complications?

What are the other anticipated side effects?

What class of drug does pazopanib belong to and what is the mechanism of action?

Cancer progression depends on a sufficient blood supply. Tumour hypoxia stimulates physiological tissue growth and the release of angiogenic growth factors to allow new blood vessel formation. Vascular endothelial growth factors (VEGFs) and receptors (VEGFRs) are key regulators of this process.1 The tyrosine kinase inhibitors (TKIs) of VEGFRs are low-molecular-weight adenosine triphosphate (ATP)-mimetic proteins that bind to the ATP-binding catalytic site of the VEGFR tyrosine kinase domain, resulting in blockade of intracellular signalling.1

Pazopanib is an orally administered, potent multi-target TKI of VEGFR1, 2 and 3, platelet-derived growth factor receptors α and β, and stem cell growth factor receptor.1

Are there others drugs in clinical use that target angiogenesis?

There are now a number of therapeutic agents available for use in clinical practice that target angiogenesis. The development of these drugs has been a major advance in the therapeutic armamentarium (Table 3.1).

Table 3.1Drugs targeting ...

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