This information is about sunitinib, also called Sutent®. It is used to treat people with a type of kidney cancer called renal cell carcinoma (RCC) and also a rare type of cancer called Gastrointestinal Stromal Tumour (GIST). Sunitinib may be used to treat other types of cancer as part of a clinical trial.
What is sunitinib?
Sunitinib is a type of drug called a multikinase inhibitor. It interferes with the growth of cancer cells. It also works by slowing the growth of new blood vessels within the tumour.
Sunitinib is used to treat people with kidney cancer (renal cell carcinoma). It is also used for people with gastrointestinal stromal tumours (GIST) that are no longer helped by the drug Imatinib.
Although sunitinib is licensed and can be prescribed in the UK, it has not yet been assessed by the National Institute for Health and Clinical Excellence (NICE). NICE gives advice on which new drugs or treatments should be available on the NHS. As a result, sunitinib may not be widely available on the NHS. Normally the only way to receive it on the NHS is if you are in a clinical trial, or if your local health authority has given special permission – known as an ETA (exceptional treatment arrangement) – This involves a lengthy application process and can be a bit of a lottery.
Sunitinib is also being studied as a possible treatment for other cancers, including melanoma, lung cancer and bowel cancer.
Multikinase inhibitors work by interfering with proteins called kinases. Kinases are important in regulating how cells work and grow. They send signals to the cell that tell it to divide and make new cells. Kinase inhibitors block these signals and affect the cancer’s ability to grow.
Some types of kinase stimulate cells to make new blood vessels. Making blood vessels is called angiogenesis. Cancer cells need to make new blood vessels so that they can grow and spread.
In kidney cancer, higher than normal amounts of a type of kinase called vascular endothelial growth factor (VEGF) are made. VEGF stimulates the production of blood vessels, and so helps the cancer to grow. Sunitinib blocks the activity of VEGF.
What sunitinib looks like
Sunitinib is an orange or caramel coloured capsule. It comes in three strengths: 50mg, 25mg and 12.5mg.
How it is given
It is taken with a glass of water. It can be taken with or without food. The usual dose is one 50mg tablet a day. A cycle of treatment is one tablet a day for four weeks followed by two weeks off. Your doctor may adjust the dose.
Possible side effects
Each person’s reaction to an anti-cancer drug is different. Some people have very few side effects, while others may experience more. If you notice any effects which you think may be due to the medicine, but we haven’t mentioned here, please discuss them with your doctor.
As sunitinib is still a new drug, it is too early to know everything about the possible side effects. Check with your doctor if any side effects continue or are troublesome.
Tiredness (fatigue) and a general feeling of weakness
Fatigue is common. It is important to allow yourself plenty of time to rest.
Hand-foot skin reaction
This is common. You may notice redness of the palms of your hands and soles of your feet. Sometimes the hands and feet become sore or swollen. There may also be changes in sensation, such as numbness or tingling. If you notice this, let your specialist know. Occasionally if soreness doesn’t settle, or if blistering develops, your doctors may need to reduce the dose of sunitinib or interrupt the treatment. Very occasionally, treatment may need to be stopped.
Your mouth may become sore, or you may notice small ulcers during this treatment. Drinking plenty of fluids and cleaning your teeth regularly can help. Some people find their mouth becomes too sensitive for regular mint toothpaste. If this happens, try a mild children’s toothpaste.
Tell your nurse or doctor if you have mouth problems. They may prescribe mouthwashes and medicines to prevent or clear any infection.
Effects on the skin and hair
Hair and skin colour can be affected by sunitinib. Your hair is likely to lose colour or become thinner. It is very unlikely that all of your hair will come out. Hair thinning is temporary. Your skin is likely to lose colour and become yellow in tone. Other changes to the skin may include a rash, redness, dryness or itching. Speak to your doctor or nurse if you have any of these symptoms. They can talk to you about creams or lotions to use to relieve any itching. They can also prescribe medicine to help relieve itching.
High blood pressure
Sunitinib can cause high blood pressure in some people. This is most likely to happen within the first few weeks of taking sunitinib. If you develop high blood pressure, your treatment may be interrupted or you may be prescribed medicine to control your blood pressure.
You may have frequent or loose bowel movements. If necessary take loperamide (imodium) tablets. Tell your doctor if these are severe or if they continue. It is important to drink plenty of fluids if you have diarrhoea.
Nausea (feeling sick)
Mild nausea is quite common but it is usually easy to control. Your doctor can prescribe anti sickness drugs to prevent or greatly reduce this.
Less common side effects
This drug may cause bleeding, most often nosebleeds. If you notice any unexplained bleeding (gums, back passage, blood in your stool, bleeding from cuts or grazes) contact your doctor straight away.
Sunitinib may cause rarely cause heart problems. If you have chest pain, shortness of breath or other symptoms that may mean that your heart is affected, contact your doctor immediately.
Sunitinib may increase your chance of getting a blood clot. If you become breathless or get pain in your limbs, tell your doctor straight away.
Sunitinib may make your thyroid work less effectively. If you feel very tired, you may need a blood test to check your thyroid levels.
Some medicines can interact with sunitinib and may make it less effective. Let your doctor know about any medicines you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs. Avoid taking St John’s Wort and grapefruit or grapefruit juice while you are having sunitinib.
It is not advisable to become pregnant or father a child while taking sunitinib, as the medicine may harm a developing foetus. It’s important to use effective contraception while taking sunitinib, and for at least a few months afterwards.
Should be avoided while taking sunitinib, as the drug may be passed to the baby in breast milk.
It is not yet known how sunitinib may affect fertility. If you have concerns about this, you can discuss them with your specialist.
Things to remember about sunitinib tablets
- Sunitinib could be harmful to children. Keep the tablets in a safe place where children cannot reach them.
- If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist. Do not flush them down the toilet or throw them away.
- If you are sick just after taking the tablets, let your doctor know, as you may need to take another dose. Do not take another tablet without first telling your doctor.
- If you forget to take a tablet do not take a double dose. Tell your doctor and keep to your regular dose schedule.
Further Information For Healthcare Professionals
ADVERSE REACTIONS SIGNIFICANT
- Cardiovascular: Hypertension (15% to 30%; grades 3/4: 4% to 10%), LVEF decreased (11% to 21%; grades 3/4: 1%), peripheral edema (11%)
- Central nervous system: Fatigue (42% to 58%), fever (17% to 18%), headache (13% to 18%), chills (11%), insomnia (11%)
- Dermatologic: Hyperpigmentation (19% to 33%), skin discoloration (19% to 30%), rash (14% to 27%), hand-foot syndrome (12% to 21%), dry skin (17% to 18%), hair color changes (7% to 16%)
- Endocrine & metabolic: Hyperuricemia (15% to 41%), hypophosphatemia (9% to 36%), hypocalcemia (35%), hypoglycemia (19%), hypoalbuminemia (18%), hyperglycemia (15%), hyponatremia (6% to 14%), hypokalemia (12%), hyperkalemia (6% to 11%), hypernatremia (10% to 11%)
- Gastrointestinal: Diarrhea (40% to 58%), lipase increased (25% to 52%), nausea (31% to 49%), taste perversion (21% to 44%), mucositis/stomatitis (29% to 43%), anorexia (31% to 38%), constipation (16% to 34%), abdominal pain (22% to 33%), dyspepsia (28%), vomiting (24% to 28%), amylase increased (5% to 17%), weight loss (12%), xerostomia (12%), GERD/reflux (11%)
- Hematologic: Leukopenia (up to 78%; grades 3/4: 5%), neutropenia (53% to 72%; grades 3/4: 10% to 12%), anemia (26% to 72%; grades 3/4: 3% to 7%), thrombocytopenia (38% to 65%; grades 3/4: 5% to 8%), lymphopenia (38% to 59%; grades 3/4: up to 59%), hemorrhage/bleeding (18% to 30%)
- Hepatic: AST increased (39% to 52%), ALT increased (39% to 46%), alkaline phosphatase increased (24% to 42%), hyperbilirubinemia (10% to 19%)
- Neuromuscular & skeletal: Creatine kinase increased (41%), weakness (21% to 22%), back pain (11% to 19%), arthralgia (12% to 18%), limb pain (14% to 17%), myalgia (14%)
- Renal: Creatinine increased (12% to 66%)
- Respiratory: Dyspnea (10% to 28%), cough (8% to 17%)
1% to 10%:
- Cardiovascular: Venous thrombotic events (2% to 3%), DVT (1% to 3%), myocardial ischemia (1%)
- Central nervous system: Depression (8%), dizziness (7%)
- Dermatologic: Skin blistering (7%), alopecia (5%)
- Endocrine & metabolic: Dehydration (8%), hypothyroidism (3% to 7%)
- Gastrointestinal: Flatulence (10%), glossodynia (10%), oral pain (6% to 10%), appetite disturbance (9%), pancreatitis (1%)
- Neuromuscular & skeletal: Peripheral neuropathy (10%)
- Ocular: Periorbital edema (7%), lacrimation increased (6%)
- Respiratory: Pulmonary embolism (1%)
<1% (Limited to important or life-threatening):
Acute renal failure, adrenal dysfunction, CHF, febrile neutropenia, gastrointestinal perforation, hepatic failure, infection, microangiopathic hemolytic anemia (when used in combination with bevacizumab), MI, myopathy, neutropenic infection, pulmonary hemorrhage, QTc prolongation (dose dependent), reversible posterior leukoencephalopathy syndrome (RPLS), rhabdomyolysis, seizure, torsade de pointes
MECHANISM OF ACTION
Exhibits antitumour and antiangiogenic properties by inhibiting multiple receptor tyrosine kinases, including platelet-derived growth factors (PDGFRalpha and PDGFRß), vascular endothelial growth factors (VEGFR1, VEGFR2, and VEGFR3), FMS-like tyrosine kinase-3 (FLT3), colony-stimulating factor type 1 (CSF-1R), and glial cell-line-derived neurotrophic factor receptor (RET).
PHARMACODYNAMICS / KINETICS
- Distribution: Vd/F: 2230 L
- Protein binding: Sunitinib: 95%; SU12662: 90%
- Metabolism: Hepatic; primarily metabolized by CYP3A4 to the N-desethyl metabolite SU12662 (active)
- Half-life elimination: Sunitinib: 40-60 hours; SU12662: 80-110 hours
- Time to peak, plasma: 6-12 hours
- Excretion: Faeces (61%); urine (16%)