Pazopanib (CAS: 444731-52-6)

Pazopanib (trade name Votrient) is a potent and selective multi-targeted receptor tyrosine kinase

inhibitor that blocks tumour growth and inhibits angiogenesis. It has been approved for renal cell

carcinoma and soft tissue sarcoma by numerous regulatory administrations worldwide.

Medical uses

It is approved by numerous regulatory administrations worldwide (including the FDA (19 October

2009), EMA (14 June 2010), MHRA (14 June 2010) andTGA (30 June 2010)) for use as a treatment

for advanced/metastatic renal cell carcinoma and advanced soft tissue sarcomas. In Australia it is

subsidised under the PBS, under a number of conditions, including:

• • The medication is used to treat clear cell variant renal cell carcinoma.
  • The treatment phase is continuing treatment beyond 3-months.
  • The patient has been issued an authority prescription for pazopanib
  • The patient must have stable or responding disease according to the Response Evaluation Criteria In Solid Tumours (RECIST)
  • This treatment must be the sole tyrosine kinase inhibitor subsidised for this condition.

It has also demonstrated initial therapeutic properties in patients with ovarian and non-small cell lung

cancer, though plans to apply to the EMA for a variation to include advanced ovarian cancer have been

withdrawn and a license will not be sought in any country.

Contraindications

The only contraindication is hypersensitivity to pazopanib or any of its excipients. Cautions include:

• • Hypertension, including hypertensive crises reported
  • QT interval prolongation and torsades de pointes reported.
  • Thrombotic microangiopathy reported
  • Thrombotic thrombocytopenic purpura reported
  • Haemolytic uremic syndrome reported
  • Haematologic parameter alterations reported in 31-37% of patients.
  • Events of cardiac dysfunction (decreased LVEF and congestive heart failure) have been observed
  • Fatal haemorrhage, arterial and venous thrombotic events and GI perforation have been observed in randomized clinical trials.

It has one black box warning by the US FDA, severe hepatotoxicity, including fatalities.

Adverse effects

See also: List of adverse effects of pazopanib

The most common side effects of pazopanib are nausea, vomiting, diarrhoea (occurs in about half of patients),

changes in hair colour, hypertension (which usually occurs during the first few weeks of treatment), appetite

loss, hyperglycaemia, hypoglycaemia, electrolyte abnormalities (includinghypocalcaemia, hypomagnesemia, 

hypophosphatemia), lab anomalies (including increased AST, ALT and protein in the urine), oedema, hair loss

or discolouration, taste changes, abdominal pain, hypertension, rash, fatigue and myelosuppression (including 

leucopenia, neutropenia,thrombocytopenia and lymphopenia). It has been associated with a low, but real risk

of potentially fatal liver damage.

Overdose

The treatment for overdose is purely supportive and the symptoms include grade 3 hypertension and fatigue.