Pazopanib

Pazopanib is an oral anticancer medicine belonging to the tyrosine kinase inhibitor class of targeted therapies. It blocks several proteins involved in tumour growth and the formation of new blood vessels, including vascular endothelial growth factor receptors, platelet-derived growth factor receptors and other kinases. By inhibiting these signalling pathways, pazopanib can reduce the blood supply that supports tumour growth and interfere with cancer-cell activity. It is primarily used to treat adults with advanced renal cell carcinoma, a type of kidney cancer, and selected forms of advanced soft-tissue sarcoma after previous chemotherapy. Unlike traditional intravenous chemotherapy, pazopanib is taken by mouth as tablets, generally once daily according to the prescribed regimen. Treatment may continue while the cancer remains controlled and the medicine is tolerated, with interruptions or dose reductions when necessary. Pazopanib is not suitable for every cancer subtype, and its benefits depend on the diagnosis, previous treatment, overall health and other medicines being taken. Liver injury is a particularly important safety concern, so liver-function testing is required before and during treatment. Blood pressure, blood counts and symptoms suggesting bleeding, clotting or other complications may also require monitoring. Treatment should be managed by an oncology specialist who can assess response, review interactions and adjust therapy when clinically indicated.

Pazopanib was developed as an orally active, multi-target tyrosine kinase inhibitor intended to interfere with signalling pathways that support tumour growth and angiogenesis. Its clinical development included studies in advanced renal cell carcinoma and previously treated soft-tissue sarcoma. The United States Food and Drug Administration first approved pazopanib in 2009 for advanced renal cell carcinoma, with a later approval for advanced soft-tissue sarcoma in patients who had received prior chemotherapy. The European Commission authorised Votrient in June 2010 for advanced renal cell carcinoma, and its European indication was subsequently extended to selected forms of advanced soft-tissue sarcoma. Regulatory authorities restrict its use according to the cancer type and clinical circumstances because effectiveness has not been established for every tumour subtype. Approval and prescribing requirements can differ between countries and products. In India, the applicable Central Drugs Standard Control Organisation status and locally approved product information should be checked before use. Clinical evidence supporting pazopanib includes randomised studies assessing disease control and progression-free survival in renal cell carcinoma and soft-tissue sarcoma.

Pazopanib is indicated for adults with advanced renal cell carcinoma and for adults with advanced soft-tissue sarcoma who have received prior chemotherapy, according to the relevant approved product information. In renal cell carcinoma, it may be used as an initial systemic treatment or in other approved treatment settings depending on local guidance and the patient's clinical history. In soft-tissue sarcoma, its use is limited to selected tumour subtypes and appropriate clinical circumstances. Pazopanib is generally administered as a single targeted therapy rather than as part of a conventional chemotherapy combination. It is not established as an effective treatment for every soft-tissue sarcoma subtype, including adipocytic soft-tissue sarcoma, or for gastrointestinal stromal tumours under the US prescribing information. Treatment decisions depend on the tumour type, disease extent, prior therapies, organ function and other individual factors. A specialist should confirm that the patient's diagnosis falls within an approved or otherwise clinically justified indication before treatment begins.

Pazopanib is administered orally as tablets. The usual adult dose in the US prescribing information for advanced renal cell carcinoma and advanced soft-tissue sarcoma is 800 mg once daily, taken without food at least one hour before or two hours after a meal. Tablets should be swallowed according to the product instructions and should not be crushed. The dose may need to be reduced or treatment temporarily interrupted because of adverse effects, liver-function abnormalities, drug interactions or other clinical concerns. The appropriate starting dose and adjustment schedule must follow the specific product information and the treating oncologist's instructions. Treatment is generally continued until disease progression or unacceptable toxicity occurs. Liver-function tests and blood pressure should be assessed before and during therapy, alongside other investigations guided by the patient's condition. Patients should not change their dose, stop treatment or compensate for a missed dose without following the prescribed instructions.

Common side effects of pazopanib include diarrhoea, nausea, vomiting, reduced appetite, fatigue, high blood pressure, changes in hair colour, altered taste, weight loss and soreness or inflammation inside the mouth. Skin changes, including rash and changes in skin pigmentation, may also occur. Laboratory tests can show increased liver enzymes, which may indicate liver irritation or injury and require clinical assessment. Some patients experience weakness, headache or abdominal discomfort. The type and severity of side effects vary between individuals and may depend on the dose, other medicines and general health. Supportive treatment, regular monitoring and medically supervised dose adjustments can help manage many adverse effects. Patients should report persistent diarrhoea, worsening fatigue, yellowing of the skin or eyes, dark urine, unusual bruising or other new symptoms promptly to their healthcare team.

Pazopanib carries an important warning for severe and potentially fatal liver injury. Liver function must be monitored regularly, and treatment may need to be interrupted, reduced or discontinued if significant abnormalities develop. Other serious risks include high blood pressure, bleeding, blood clots, heart dysfunction, abnormal heart rhythms, gastrointestinal perforation or fistula, impaired wound healing and a rare neurological condition called posterior reversible encephalopathy syndrome. Protein in the urine and thyroid dysfunction may also occur. Patients undergoing major surgery may require a planned treatment interruption because pazopanib can impair wound healing. Severe or persistent abdominal pain, chest pain, sudden breathlessness, significant bleeding, severe headache with visual changes, or symptoms of liver injury require urgent medical assessment. Treatment should be withheld or discontinued when clinically significant toxicity warrants it, following the approved prescribing information. Patients should not stop or restart pazopanib without guidance from their oncology team.

Before starting pazopanib, clinicians should assess liver function, blood pressure, cardiovascular history, bleeding risk, kidney function and relevant urine findings. Additional evaluation may be needed for patients with pre-existing liver disease, heart conditions, clotting disorders or recent surgery. Pregnancy should be avoided during treatment because pazopanib may harm a developing fetus; appropriate contraception and fertility counselling should be discussed. Breastfeeding should be avoided according to the applicable product information. Pazopanib is metabolised mainly through CYP3A4, so strong inhibitors or inducers of this enzyme can alter its concentration and effectiveness. Certain medicines that prolong the QT interval or increase bleeding risk may require particular caution. Acid-reducing medicines, including proton pump inhibitors and H2-receptor antagonists, can reduce pazopanib absorption; alternatives or administration adjustments should be considered by the prescriber. Grapefruit and grapefruit products should be avoided because they may affect drug exposure. Patients should disclose all prescription medicines, over-the-counter products, herbal preparations and supplements before treatment. Live vaccines and vaccination timing should be reviewed with the treating team, particularly when other immunosuppressive treatments are involved.

Confirm the indication, baseline liver-function results, blood pressure and complete medication list before initiating pazopanib. Reinforce the fasting administration requirement and advise patients to swallow tablets whole according to the product instructions. Establish a schedule for liver-function monitoring, particularly during the early months of treatment, and continue monitoring as clinically indicated. Check blood pressure regularly and manage hypertension promptly. Review CYP3A4 interactions, acid-reducing medicines, QT-prolonging agents and medicines that increase bleeding risk. Assess for proteinuria, thyroid dysfunction, cardiovascular complications and symptoms of gastrointestinal injury when appropriate. Before planned surgery, coordinate with the surgical and oncology teams regarding treatment interruption and restarting, taking wound healing into account. Counsel patients to report jaundice, unusual bleeding, severe abdominal pain, chest pain or neurological symptoms urgently. Record adverse effects and treatment interruptions clearly, and use the approved dose-modification guidance when toxicity develops. Pharmacists should also confirm storage requirements, tablet integrity and adherence instructions, while the oncology team should regularly evaluate treatment response and overall tolerability.