Sunitinib

Sunitinib is an oral targeted anticancer medicine belonging to the tyrosine kinase inhibitor class. It blocks several receptor tyrosine kinases involved in tumour growth, blood vessel formation and the signalling pathways that support cancer cell survival. Its targets include vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), KIT and other kinases. By inhibiting these pathways, sunitinib can slow tumour growth and reduce the blood supply that supports certain cancers. It is used in adults with selected cancers, including advanced renal cell carcinoma, gastrointestinal stromal tumours that have progressed during or cannot tolerate imatinib, and progressive pancreatic neuroendocrine tumours that cannot be removed surgically or have spread. In the United States, it is also approved as adjuvant treatment for selected adults at high risk of recurrent renal cell carcinoma following kidney removal. Sunitinib is taken by mouth, usually once daily, with the schedule depending on the condition being treated. Because it can affect the liver, heart, blood pressure, thyroid function and blood cell counts, treatment requires regular clinical and laboratory monitoring. The dose or treatment schedule may need adjustment according to adverse effects, overall health and response to therapy.

Sunitinib was developed as a targeted therapy to inhibit receptor tyrosine kinases involved in tumour growth and angiogenesis. The United States Food and Drug Administration (FDA) initially approved sunitinib in January 2006 for advanced renal cell carcinoma and gastrointestinal stromal tumours following progression on or intolerance to imatinib. Its use was subsequently expanded to progressive, unresectable or metastatic pancreatic neuroendocrine tumours. In the United States, approval also covers adjuvant treatment for adults at high risk of recurrent renal cell carcinoma after nephrectomy. The European Commission granted marketing authorisation for Sutent on 19 July 2006, with approved indications including gastrointestinal stromal tumours after imatinib failure or intolerance, advanced or metastatic renal cell carcinoma, and progressive, unresectable or metastatic well-differentiated pancreatic neuroendocrine tumours. Key clinical development programmes included studies of sunitinib in imatinib-resistant gastrointestinal stromal tumours, advanced renal cell carcinoma and pancreatic neuroendocrine tumours. These studies established its role as a targeted treatment for selected cancers. Approved indications and dosing recommendations vary by jurisdiction, so current local prescribing information should be consulted before treatment.

Sunitinib is used to treat adults with gastrointestinal stromal tumours (GIST) that cannot be removed surgically or have spread, when the disease progresses during imatinib treatment or the patient cannot tolerate imatinib. It is also indicated for advanced or metastatic renal cell carcinoma, a type of kidney cancer. In the United States, sunitinib is approved as adjuvant treatment for selected adults at high risk of recurrent renal cell carcinoma following nephrectomy; this indication may not be approved in every country. Another approved use is progressive, well-differentiated pancreatic neuroendocrine tumours that are unresectable, locally advanced or metastatic. Treatment selection depends on tumour type, disease stage, previous therapy, general health and the applicable regulatory indication. Sunitinib is generally used as a single anticancer agent, although supportive medicines may be needed to manage symptoms or treatment-related adverse effects. It should be prescribed by an oncology specialist familiar with targeted cancer therapies.

Sunitinib is administered orally as capsules and may generally be taken with or without food. For gastrointestinal stromal tumours and advanced renal cell carcinoma, the standard adult regimen is commonly 50 mg once daily for four weeks, followed by a two-week treatment break, forming a six-week cycle. For adjuvant treatment of renal cell carcinoma in the United States, the usual regimen is the same four-weeks-on, two-weeks-off schedule for up to nine cycles. For progressive pancreatic neuroendocrine tumours, the usual adult dose is 37.5 mg once daily on a continuous schedule without a planned treatment break. The prescribed dose may be reduced or treatment temporarily interrupted according to tolerability, laboratory results and adverse effects. Patients should take the medicine consistently as directed and should not change the dose or schedule themselves. Treatment duration depends on the indication, clinical response, disease progression and safety. Regular blood tests, blood pressure checks, liver assessment and evaluation for other treatment-related complications are important throughout therapy.

Common side effects of sunitinib include fatigue, diarrhoea, nausea, vomiting, reduced appetite, abdominal discomfort and changes in taste. Patients may develop mouth sores, skin discolouration, rash, dry skin or hand-foot syndrome, which can cause redness, swelling, tenderness or peeling of the palms and soles. High blood pressure, low thyroid function, changes in blood cell counts and altered liver enzyme levels may also occur. Some patients experience swelling, weight changes or reduced energy levels. Side effects vary between individuals and may depend on the dose, treatment schedule and underlying cancer. Many can be managed with supportive care, monitoring and appropriate treatment adjustments. Patients should report persistent or worsening symptoms to their healthcare team, particularly when they interfere with eating, drinking, daily activities or medication adherence.

Sunitinib can cause serious liver injury, including rare cases of liver failure, and liver function must be monitored before and during treatment. Other important risks include heart failure, reduced left ventricular function, abnormal heart rhythms, QT interval prolongation, severe hypertension, bleeding, blood clots and gastrointestinal perforation. Kidney complications, including proteinuria and impaired kidney function, may occur. The medicine can also cause low blood cell counts, thyroid dysfunction, low blood sugar, impaired wound healing and, rarely, osteonecrosis of the jaw. Patients should seek urgent medical attention for chest pain, severe breathlessness, fainting, significant bleeding, black stools, severe abdominal pain, jaundice or sudden neurological symptoms. Treatment may need to be withheld, reduced or permanently discontinued depending on the nature and severity of toxicity. Blood pressure should be controlled before and during treatment, and significant liver injury requires prompt assessment. Surgical procedures may require a planned interruption because sunitinib can impair wound healing. Any interruption or discontinuation should be managed by the treating oncology team.

Before starting sunitinib, clinicians should review cardiovascular disease, hypertension, liver or kidney impairment, bleeding disorders, thyroid problems, diabetes, previous thromboembolic events and planned surgery or dental procedures. Baseline assessments generally include blood pressure, complete blood count, liver and kidney function, thyroid function, electrolytes and urine protein assessment. Cardiac evaluation, including an electrocardiogram or assessment of ventricular function, may be needed for patients with relevant risk factors. Sunitinib is metabolised primarily through the CYP3A4 pathway, so strong CYP3A4 inhibitors can increase drug exposure, while strong inducers can reduce exposure and potentially affect efficacy. Examples include certain azole antifungals, macrolide antibiotics, rifampicin and some seizure medicines; alternative medicines or dose adjustments may be necessary under specialist supervision. Grapefruit products may also affect CYP3A4 activity and should be discussed with the treating team. Anticoagulants and medicines that affect heart rhythm or blood pressure require careful review. Pregnancy should be avoided during treatment because sunitinib may harm a developing fetus; contraception and breastfeeding precautions should be discussed with the healthcare professional.

Confirm the indication, treatment schedule and capsule strength before dispensing or prescribing sunitinib. Establish baseline blood pressure, blood counts, liver and kidney function, thyroid function and urine protein, with additional cardiac testing where clinically indicated. Review all prescription medicines, over-the-counter products, supplements and dietary products for CYP3A4 interactions. Counsel patients to take capsules consistently, follow the prescribed schedule and never compensate for a missed dose by doubling the next dose. Explain early signs of hand-foot syndrome, mouth sores, diarrhoea, hypertension, bleeding and liver injury, and provide clear instructions on when to contact the oncology team urgently. Monitor blood pressure regularly and repeat laboratory tests according to the regimen and the patient's clinical status. Assess thyroid function periodically and investigate unexplained fatigue, weight changes or temperature sensitivity. Before elective surgery or invasive dental procedures, coordinate with the oncology team regarding possible treatment interruption and wound-healing risks. Pharmacists should reinforce adherence, check for treatment-related interactions and support timely reporting of adverse effects. Treatment modifications should follow the current prescribing information and the patient's clinical response.