Pazopanib
Overview
Pazopanib is an orally administered small-molecule tyrosine kinase inhibitor classified as an anti-angiogenic targeted therapy. It works by inhibiting multiple receptor tyrosine kinases involved in tumour growth and blood vessel formation, including vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-kit. By blocking these signalling pathways, pazopanib reduces angiogenesis, which is essential for tumour nourishment and progression. This mechanism makes it clinically important in certain advanced solid tumours where angiogenesis plays a key role in disease progression. Pazopanib is used in adult oncology practice and is administered as a once-daily oral tablet, allowing outpatient management. Despite its convenience, it requires careful clinical oversight due to its effects on liver function, blood pressure, cardiac conduction, and other systemic processes. Appropriate patient selection and ongoing monitoring are essential to balance therapeutic benefit with potential risks. Pazopanib has become an established option in targeted cancer therapy where disease control and quality of life considerations are important components of treatment planning.
Background and Date of Approval
Pazopanib was developed as a multi-targeted tyrosine kinase inhibitor aimed at suppressing tumour angiogenesis. It received its first regulatory approval from the United States Food and Drug Administration on 19 October 2009 for the treatment of advanced and metastatic renal cell carcinoma. Subsequently, the European Medicines Agency granted approval on 14 June 2010, expanding its regulatory recognition within Europe, including its use in advanced soft tissue sarcoma. These approvals were supported by pivotal phase III clinical trials that demonstrated improvements in progression-free survival in advanced renal cell carcinoma and clinically meaningful activity in soft tissue sarcoma following prior chemotherapy. The regulatory history established pazopanib as a standard targeted therapy option in these indications.
Uses
Pazopanib is indicated for the treatment of adults with advanced renal cell carcinoma and for adults with advanced soft tissue sarcoma who have previously received chemotherapy. In these conditions, it is generally used as monotherapy to slow tumour progression and manage disease burden. Its use is guided by tumour type, prior treatment history, patient performance status, and organ function. Pazopanib is not intended for use in early-stage disease and is reserved for advanced or metastatic settings where systemic targeted therapy is appropriate.
Administration
Pazopanib is administered orally as a tablet and is typically prescribed at a standard dose of 800 mg once daily. It should be taken on an empty stomach, at least one hour before or two hours after food, to ensure consistent absorption. Dose modifications may be required in patients with hepatic impairment or in those experiencing treatment-related toxicities. Therapy is generally continued until disease progression or unacceptable adverse effects occur. Regular monitoring of liver function, blood pressure, and overall tolerability is an integral part of dosing management.
Side Effects
Commonly reported side effects of pazopanib include diarrhea, nausea, vomiting, fatigue, loss of appetite, headache, taste disturbances, and changes in hair or skin colour. Elevated blood pressure is also frequently observed. The intensity and combination of side effects vary among individuals and are often manageable with dose adjustments, supportive care, and close medical supervision.
Warnings
Pazopanib is associated with serious adverse events, most notably severe hepatotoxicity, which can be life-threatening. Other significant risks include cardiac dysfunction, QT interval prolongation, arterial and venous thrombotic events, gastrointestinal perforation, and severe hypertension. Rare neurological conditions such as posterior reversible encephalopathy syndrome have also been reported. Pazopanib can cause fetal harm and is contraindicated during pregnancy, with treatment interruption or discontinuation required in cases of severe toxicity.
Precautions
Baseline assessment of liver function, blood pressure, and cardiac status is essential before initiating pazopanib. Caution is required in patients with pre-existing liver disease or cardiovascular risk factors. Pazopanib is metabolised through hepatic pathways and may interact with strong inhibitors or inducers of drug-metabolising enzymes, necessitating dose adjustment or avoidance. Use during pregnancy or breastfeeding is not recommended, and effective contraception is advised during treatment.
Expert Tips
Careful patient selection based on indication, liver function, and cardiovascular risk profile is crucial when prescribing pazopanib. Baseline and periodic liver function tests should be performed, along with regular blood pressure monitoring. Patients should be counselled on correct administration timing relative to meals and advised to report symptoms such as jaundice, severe fatigue, chest pain, or neurological changes promptly. Coordination with other oncology therapies and supportive medications helps minimise overlapping toxicities and interactions.