It is approved by numerous regulatory administrations worldwide (including the FDA (19 October 2009), EMA (14 June 2010), MHRA (14 June 2010) and TGA (30 June 2010)) for use as a treatment for advanced/metastatic renal cell carcinoma and advanced soft tissue sarcomas. In Australia and New Zealand, it is subsidised under the PBS and by Pharmac respectively, 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cell lung cancer, though plans to apply to the EMA for a variation to include advanced ovarian cancer have been withdrawn and a license will not be sought in any country.
The only contraindication is hypersensitivity to pazopanib or any of its excipients. Cautions include:
Hypertension, including hypertensive crises reported
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 (including hypocalcaemia, hypomagnesemia, hypophosphatemia), lab anomalies (including increased AST, ALT and protein in the urine), oedema, hair loss or discolouration, taste changes, abdominal pain, 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.
The treatment for overdose is purely supportive and the symptoms include grade 3 hypertension and fatigue.
Pazopanib have inhibitory potency towards OATP-1B1 but not for OATP-1B3.
Mechanism of action
Pazopanib is a multikinase inhibitor that limits tumor growth by targeting angiogenesis via inhibition of enzymes including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factory receptor (PDGFR), c-KIT and FGFR.
^ abcZivi, A; Cerbone, L; Recine, F; Sternberg, CN (September 2012). "Safety and tolerability of pazopanib in the treatment of renal cell carcinoma". Expert Opinion on Drug Safety. 11 (5): 851–859. doi:10.1517/14740338.2012.712108. PMID22861374.