sorafenib
Multikinase inhibitor· Brands: NexavarPO
Mechanism of action
Sorafenib is a multikinase inhibitor that blocks tumour cell proliferation and angiogenesis. It inhibits RAF kinases (including C-RAF and B-RAF), VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-beta, KIT, FLT-3, and RET. By inhibiting these pathways, it reduces tumour growth and disrupts tumour blood supply.
Pharmacokinetics
Its bioavailability is approximately 38–49% and is reduced by a high-fat meal (about 29% versus the fasted state), so the tablets are taken at least one hour before or two hours after food.
Indications & dosing
Hepatocellular carcinoma (advanced, unresectable)
Taken continuously until disease progression or unacceptable toxicity.
- adult · PO: 400 mg twice daily · Taken continuously until disease progression or unacceptable toxicity.
Renal cell carcinoma (advanced)
Taken continuously until disease progression or unacceptable toxicity.
- adult · PO: 400 mg twice daily · Taken continuously until disease progression or unacceptable toxicity.
Differentiated thyroid carcinoma (refractory to radioiodine)
Taken continuously until disease progression or unacceptable toxicity.
- adult · PO: 400 mg twice daily · Taken continuously until disease progression or unacceptable toxicity.
Contraindications & precautions
- Known hypersensitivity to sorafenib or any component of the formulation · Avoid in patients with previous allergic reaction.
- Severe hepatic impairment (Child-Pugh C) · Sorafenib is not recommended in severe hepatic impairment.
- Pregnancy · Teratogenic; effective contraception needed during treatment.
- Monitor blood pressure regularly, especially during the first 6 weeks of treatment; manage hypertension with antihypertensives as needed.
- Monitor patients for bleeding, especially those with recent surgery or receiving anticoagulants.
- Monitor hepatic function before and during treatment; sorafenib is contraindicated in severe hepatic impairment.
- Use with caution in patients with renal impairment; dose adjustment may be required.
- Monitor electrocardiogram in patients at risk of QT prolongation.
- Monitor symptoms of hand-foot skin reaction; provide supportive care and consider dose interruption or reduction.
Adverse effects
- Hand-foot skin reaction
- Diarrhoea
- Hypertensionserious
- Fatigue
- Nausea
- Haemorrhageserious
- Cardiac ischaemiaserious
- QT interval prolongationserious
- Hepatotoxicityserious
Renal & hepatic adjustment
- eGFR 0+: No dose adjustment required. Use caution in severe renal impairment due to limited data.
- Hepatic impairment (mild): No dose adjustment required.
- Hepatic impairment (moderate): No dose adjustment required.
- Hepatic impairment (severe): Not recommended. Avoid use in severe hepatic impairment (Child-Pugh C). (avoid)
Monitoring, pregnancy & toxicity
- Blood pressure · Regularly during treatment
- Hand-foot syndrome · At each visit
- Liver function tests · At baseline and periodically
- Renal function and electrolytes · At baseline and periodically
- Full blood count · At baseline and periodically
- INR, if receiving anticoagulants · Regularly
- Pregnancy: Sorafenib is contraindicated during pregnancy. Women of childbearing potential should use effective contraception during treatment and for at least 3 months after stopping sorafenib.
- Toxicity: Palmar-plantar erythrodysesthesia (hand-foot syndrome) · Use topical emollients; consider dose reduction or interruption. Withhold or discontinue for severe reaction.
- Toxicity: Hypertension · Monitor blood pressure; treat with standard antihypertensives. Reduce dose or interrupt if hypertension persists.
- Toxicity: Diarrhoea · Maintain hydration; use antidiarrhoeal agents. Reduce dose for persistent grade 3 diarrhoea.
- Toxicity: Cardiac ischaemia and bleeding · Evaluate risk factors; monitor for symptoms. Discontinue treatment if serious cardiac ischaemia or bleeding occurs.
Clinical notes
Sorafenib is used in advanced renal cell carcinoma, hepatocellular carcinoma, and differentiated thyroid cancer. The usual dose is 400 mg twice daily on an empty stomach or with a moderate to low fat meal. Monitor for hand-foot skin reaction, hypertension, diarrhoea, and bleeding. Avoid in severe hepatic impairment and use caution with CYP3A4 inducers or inhibitors.
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BNF; local formulary