Sorafenib is used to treat people with renal cell carcinoma (RCC) – kidney cancer. and also hepatocellular carcinoma (HCC), a type of primary liver cancer.
Sorafenib is a type of drug called a multi-targeted kinase inhibitor. It interferes with the growth of cancer cells. It also works by slowing the growth of new blood vessels within the tumour. It is NOT a chemotherapy drug. It is a targeted ‘magic bullet’ type of therapy.
It is used to treat people with kidney cancer that has spread outside the kidney.
Hepatocellular carcinoma is the commonest type of primary liver cancer (cancer that starts in the liver). Sorafenib can be used when the cancer cannot be removed with surgery.
Although sorafenib 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, sorafenib may not be widely available on the NHS. Sorafenib is also being studied as a possible treatment for many other cancers. 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.
What sorafenib looks like
Sorafenib is a red, round tablet.
How it is given
Sorafenib should be taken on an empty stomach with a glass of water, at least one hour before or two hours after a meal. It is usually taken twice a day in a dose of 400mg.
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.
The side effects of sorafenib are generally mild and may go away during treatment as your body adjusts to the medicine.
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 of 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 sorafenib or interrupt the treatment. Very occasionally, people may need to stop having the treatment completely.
Effects on the skin
Changes in the skin such as a rash, redness, dryness or itching are quite common. These side effects are usually mild. Speak to your doctor or nurse if you have any of these symptoms. They can advise you about creams or lotions to use, or prescribe medicines to relieve itching.
High blood pressure
Sorafenib can cause high blood pressure in some people. If this develops, it is most likely to happen within the first few weeks of taking the drug. Your blood pressure will be checked every week for the first six weeks of treatment. If you develop high blood pressure you may be prescribed medicines to control this.
Tiredness (fatigue) and a general feeling of weakness
This is common, but usually mild. It’s important to allow yourself plenty of time to rest.
Diarrhoea
You may have frequent or loose bowel movements. Tell your doctor if this is severe or if it continues. It’s important to drink plenty of fluids if you have diarrhoea.
Sore mouth and ulcers
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. Tell your nurse or doctor if you have mouth problems. They may prescribe mouthwashes and medicines to prevent or clear any mouth infection.
Feeling sick (nausea)
Mild nausea is quite common, but is usually easy to control. Your doctor can prescribe effective anti-sickness drugs to prevent or greatly reduce this.
Constipation
It usually helps to drink plenty of fluids, eat a high fibre diet and take gentle exercise. Sometimes you may need to take medicines to stimulate your bowel. Your doctor can prescribe these.
Thinning hair
Rare. You may notice your hair becomes thinner. It is very unlikely all of your hair will fall out. Hair loss is temporary and the hair re-grows once treatment has finished.
Hoarseness
You may develop hoarseness or a husky voice.
Muscle pains (arthralgia)
Some people have muscle, joint or bone pain while on treatment. Your doctor can prescribe painkillers if you are affected.
Less common side effects
Bleeding problems
Sorafenib may increase your chance of bleeding. This is a less common side effect and can affect people in different ways. For example, your gums may bleed, or you may bruise more easily or notice blood in your urine or stools. If you notice any unusual bleeding contact your doctor immediately.
Heart problems
This drug may occasionally cause problems with the blood supply to the heart. If you have chest pain, shortness of breath or other symptoms that may mean your heart is affected, contact your doctor immediately.
Contraception
It is not advisable to become pregnant or father a child while taking sorafenib, as the drug may harm a developing foetus. It is important to use effective contraception while taking this drug, and for at least a few months afterwards.
Fertility
It is not yet known how sorafenib may affect fertility.
Things to remember about sorafenib tablets
- 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
>10%:
- Cardiovascular: Hypertension (9% to 17%; grade 3: 3% to 4%; grade 4: <1%; onset: ~3 weeks)
- Central nervous system: Fatigue (37% to 46%), sensory neuropathy (=13%), pain (11%)
- Dermatologic: Rash/desquamation (19% to 40%; grade 3: =1%), hand-foot syndrome (21% to 30%; grade 3: 6% to 8%), alopecia (14% to 27%), pruritus (14% to 19%), dry skin (10% to 11%), erythema
- Endocrine & metabolic: Hypoalbuminemia (=59%), hypophosphatemia (35% to 45%; grade 3: 11% to 13%; grade 4: <1%)
- Gastrointestinal: Diarrhoea (43% to 55%; grade 3: 2% to 10%; grade 4: <1%), lipase increased (40% to 41% [usually transient]), amylase increased (30% to 34% [usually transient]), abdominal pain (11% to 31%), weight loss (10% to 30%), anorexia (16% to 29%), nausea (23% to 24%), vomiting (15% to 16%), constipation (14% to 15%)
- Hematologic: Lymphopenia (23% to 47%; grades 3/4: =13%), thrombocytopenia (12% to 46%; grades 3/4: 1% to 4%), INR increased (=42%), neutropenia (=18%; grades 3/4: =5%), hemorrhage (15% to 18%; grade 3: 2% to 3%; grade 4: =2%), leukopenia
- Hepatic: Liver dysfunction (=11%; grade 3: 2%; grade 4: 1%)
- Neuromuscular & skeletal: Muscle pain, weakness
- Respiratory: Dyspnea (=14%), cough (=13%)
1% to 10%:
- Cardiovascular: Cardiac ischemia/infarction (=3%), flushing
- Central nervous system: Headache (=10%), depression, fever
- Dermatologic: Acne, exfoliative dermatitis
- Gastrointestinal: Appetite decreased, dyspepsia, dysphagia, esophageal varices bleeding (2%), glossodynia, mucositis, stomatitis, xerostomia
- Genitourinary: Erectile dysfunction
- Hematologic: Anaemia
- Hepatic: Transaminases increased (transient)
- Neuromuscular & skeletal: Joint pain (=10%), arthralgia, myalgia
- Respiratory: Hoarseness
- Miscellaneous: Influenza-like symptoms
<1% (Limited to important or life-threatening):
Acute renal failure, alkaline phosphatase increased, arrhythmia, bilirubin increased, bone pain, cardiac failure, cerebral hemorrhage, CHF, dehydration, eczema, epistaxis, erythema multiforme, folliculitis, gastritis, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal reflux, gynecomastia, hypersensitivity (skin reaction, urticaria), hypertensive crisis, hyponatremia, hypothyroidism, infection, jaundice, MI, mouth pain, myocardial ischemia, pancreatitis, pleural effusion, preeclampsia-like syndrome (reversible hypertension and proteinuria), renal failure, respiratory hemorrhage, reversible posterior leukoencephalopathy syndrome (RPLS), rhinorrhea, skin cancer (squamous cell/keratoacanthomas), thromboembolism, tinnitus, transient ischemic attack, tumor pain, voice alteration
MECHANISM OF ACTION
Multikinase inhibitor; inhibits tumour growth and angiogenesis by inhibiting intracellular Raf kinases (CRAF, BRAF, and mutant BRAF), and cell surface kinase receptors (VEGFR-2, VEGFR-3, PDGFR-beta, cKIT, and FLT-3)
PHARMACODYNAMICS / KINETICS
- Protein binding: 99.5%
- Metabolism: Hepatic, via CYP3A4 (primarily oxidated to the pyridine N-oxide; active, minor) and UGT1A9 (glucuronidation)
- Bioavailability: 38% to 49%; reduced when administered with a high-fat meal
- Half-life elimination: 25-48 hours
- Time to peak, plasma: ~3 hours
- Excretion: Faeces (77%, 51% as unchanged drug); urine (19%, as metabolites)
Sorafenib is used to treat people with renal cell carcinoma (RCC) – kidney cancer. and also hepatocellular carcinoma (HCC), a type of primary liver cancer.
Sorafenib is a type of drug called a multi-targeted kinase inhibitor. It interferes with the growth of cancer cells. It also works by slowing the growth of new blood vessels within the tumour. It is NOT a chemotherapy drug. It is a targeted ‘magic bullet’ type of therapy.
It is used to treat people with kidney cancer that has spread outside the kidney.
Hepatocellular carcinoma is the commonest type of primary liver cancer (cancer that starts in the liver). Sorafenib can be used when the cancer cannot be removed with surgery.
Although sorafenib 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, sorafenib may not be widely available on the NHS. Sorafenib is also being studied as a possible treatment for many other cancers. 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.
What sorafenib looks like
Sorafenib is a red, round tablet.
How it is given
Sorafenib should be taken on an empty stomach with a glass of water, at least one hour before or two hours after a meal. It is usually taken twice a day in a dose of 400mg.
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.
The side effects of sorafenib are generally mild and may go away during treatment as your body adjusts to the medicine.
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 of 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 sorafenib or interrupt the treatment. Very occasionally, people may need to stop having the treatment completely.
Effects on the skin
Changes in the skin such as a rash, redness, dryness or itching are quite common. These side effects are usually mild. Speak to your doctor or nurse if you have any of these symptoms. They can advise you about creams or lotions to use, or prescribe medicines to relieve itching.
High blood pressure
Sorafenib can cause high blood pressure in some people. If this develops, it is most likely to happen within the first few weeks of taking the drug. Your blood pressure will be checked every week for the first six weeks of treatment. If you develop high blood pressure you may be prescribed medicines to control this.
Tiredness (fatigue) and a general feeling of weakness
This is common, but usually mild. It’s important to allow yourself plenty of time to rest.
Diarrhoea
You may have frequent or loose bowel movements. Tell your doctor if this is severe or if it continues. It’s important to drink plenty of fluids if you have diarrhoea.
Sore mouth and ulcers
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. Tell your nurse or doctor if you have mouth problems. They may prescribe mouthwashes and medicines to prevent or clear any mouth infection.
Feeling sick (nausea)
Mild nausea is quite common, but is usually easy to control. Your doctor can prescribe effective anti-sickness drugs to prevent or greatly reduce this.
Constipation
It usually helps to drink plenty of fluids, eat a high fibre diet and take gentle exercise. Sometimes you may need to take medicines to stimulate your bowel. Your doctor can prescribe these.
Thinning hair
Rare. You may notice your hair becomes thinner. It is very unlikely all of your hair will fall out. Hair loss is temporary and the hair re-grows once treatment has finished.
Hoarseness
You may develop hoarseness or a husky voice.
Muscle pains (arthralgia)
Some people have muscle, joint or bone pain while on treatment. Your doctor can prescribe painkillers if you are affected.
Less common side effects
Bleeding problems
Sorafenib may increase your chance of bleeding. This is a less common side effect and can affect people in different ways. For example, your gums may bleed, or you may bruise more easily or notice blood in your urine or stools. If you notice any unusual bleeding contact your doctor immediately.
Heart problems
This drug may occasionally cause problems with the blood supply to the heart. If you have chest pain, shortness of breath or other symptoms that may mean your heart is affected, contact your doctor immediately.
Contraception
It is not advisable to become pregnant or father a child while taking sorafenib, as the drug may harm a developing foetus. It is important to use effective contraception while taking this drug, and for at least a few months afterwards.
Fertility
It is not yet known how sorafenib may affect fertility.
Things to remember about sorafenib tablets
- 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
>10%:
- Cardiovascular: Hypertension (9% to 17%; grade 3: 3% to 4%; grade 4: <1%; onset: ~3 weeks)
- Central nervous system: Fatigue (37% to 46%), sensory neuropathy (=13%), pain (11%)
- Dermatologic: Rash/desquamation (19% to 40%; grade 3: =1%), hand-foot syndrome (21% to 30%; grade 3: 6% to 8%), alopecia (14% to 27%), pruritus (14% to 19%), dry skin (10% to 11%), erythema
- Endocrine & metabolic: Hypoalbuminemia (=59%), hypophosphatemia (35% to 45%; grade 3: 11% to 13%; grade 4: <1%)
- Gastrointestinal: Diarrhoea (43% to 55%; grade 3: 2% to 10%; grade 4: <1%), lipase increased (40% to 41% [usually transient]), amylase increased (30% to 34% [usually transient]), abdominal pain (11% to 31%), weight loss (10% to 30%), anorexia (16% to 29%), nausea (23% to 24%), vomiting (15% to 16%), constipation (14% to 15%)
- Hematologic: Lymphopenia (23% to 47%; grades 3/4: =13%), thrombocytopenia (12% to 46%; grades 3/4: 1% to 4%), INR increased (=42%), neutropenia (=18%; grades 3/4: =5%), hemorrhage (15% to 18%; grade 3: 2% to 3%; grade 4: =2%), leukopenia
- Hepatic: Liver dysfunction (=11%; grade 3: 2%; grade 4: 1%)
- Neuromuscular & skeletal: Muscle pain, weakness
- Respiratory: Dyspnea (=14%), cough (=13%)
1% to 10%:
- Cardiovascular: Cardiac ischemia/infarction (=3%), flushing
- Central nervous system: Headache (=10%), depression, fever
- Dermatologic: Acne, exfoliative dermatitis
- Gastrointestinal: Appetite decreased, dyspepsia, dysphagia, esophageal varices bleeding (2%), glossodynia, mucositis, stomatitis, xerostomia
- Genitourinary: Erectile dysfunction
- Hematologic: Anaemia
- Hepatic: Transaminases increased (transient)
- Neuromuscular & skeletal: Joint pain (=10%), arthralgia, myalgia
- Respiratory: Hoarseness
- Miscellaneous: Influenza-like symptoms
<1% (Limited to important or life-threatening):
Acute renal failure, alkaline phosphatase increased, arrhythmia, bilirubin increased, bone pain, cardiac failure, cerebral hemorrhage, CHF, dehydration, eczema, epistaxis, erythema multiforme, folliculitis, gastritis, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal reflux, gynecomastia, hypersensitivity (skin reaction, urticaria), hypertensive crisis, hyponatremia, hypothyroidism, infection, jaundice, MI, mouth pain, myocardial ischemia, pancreatitis, pleural effusion, preeclampsia-like syndrome (reversible hypertension and proteinuria), renal failure, respiratory hemorrhage, reversible posterior leukoencephalopathy syndrome (RPLS), rhinorrhea, skin cancer (squamous cell/keratoacanthomas), thromboembolism, tinnitus, transient ischemic attack, tumor pain, voice alteration
MECHANISM OF ACTION
Multikinase inhibitor; inhibits tumour growth and angiogenesis by inhibiting intracellular Raf kinases (CRAF, BRAF, and mutant BRAF), and cell surface kinase receptors (VEGFR-2, VEGFR-3, PDGFR-beta, cKIT, and FLT-3)
PHARMACODYNAMICS / KINETICS
- Protein binding: 99.5%
- Metabolism: Hepatic, via CYP3A4 (primarily oxidated to the pyridine N-oxide; active, minor) and UGT1A9 (glucuronidation)
- Bioavailability: 38% to 49%; reduced when administered with a high-fat meal
- Half-life elimination: 25-48 hours
- Time to peak, plasma: ~3 hours
- Excretion: Faeces (77%, 51% as unchanged drug); urine (19%, as metabolites)