Sunitinib

Sunitinib (SUTENT®)

🔴 Red Flag (Important) Information

• Cardiotoxicity risk → can cause ↓ LVEF, heart failure, myocardial ischaemia, QT prolongation and torsades de pointes.
  Baseline and ongoing cardiac monitoring required, especially in patients with cardiac risk factors.

• Severe bleeding risk → GI, pulmonary, tumour, urinary tract and intracranial haemorrhage reported (some fatal).

• Hepatotoxicity → liver failure (including fatal cases) reported.
  Monitor ALT, AST and bilirubin before treatment and during each cycle.

• Hypertension → very common; may be severe and require treatment interruption.

• Thrombotic microangiopathy (TMA) including TTP/HUS → permanently discontinue if suspected.

• Impaired wound healing → interrupt treatment before major surgery.

• Osteonecrosis of the jaw (ONJ) → increased risk with prior or concurrent IV bisphosphonates.

• QT prolongation → avoid strong CYP3A4 inhibitors; correct electrolytes.

• Pregnancy and breastfeeding contraindicated → teratogenic; effective contraception required.

🔹 1. Basic Information

Generic name: Sunitinib (as sunitinib malate)
Trade name: SUTENT®
Formulation: Hard oral capsules
Strengths: 12.5 mg, 25 mg, 50 mg
Drug class: Multi-targeted tyrosine kinase inhibitor (TKI)

Mechanism of Action:
Inhibits multiple receptor tyrosine kinases involved in tumour growth, angiogenesis and metastasis, including:

• VEGFR-1, VEGFR-2, VEGFR-3

• PDGFR-α and PDGFR-β

• KIT

• FLT3

• CSF-1R

• RET

Result → inhibition of tumour proliferation and tumour angiogenesis.

🔹 2. FULL Therapeutic Indications (as per PI)

Gastrointestinal Stromal Tumour (GIST)

SUTENT is indicated for the treatment of gastrointestinal stromal tumour (GIST) after failure of imatinib mesylate treatment due to:

• Resistance, or

• Intolerance.

Metastatic Renal Cell Carcinoma (MRCC)

SUTENT is indicated for the treatment of:

1. Treatment-naïve advanced and/or metastatic renal cell carcinoma, and

2. Metastatic renal cell carcinoma after failure of cytokine-based therapy, including:

   • Interferon-α

   • Interleukin-2

Efficacy is based on:

• Time to tumour progression, and

• Increased survival.

Pancreatic Neuroendocrine Tumours (pNET)

SUTENT is indicated for the treatment of:

• Unresectable or metastatic,

• Well-differentiated pancreatic neuroendocrine tumours,

• With disease progression,

• In adult patients.

🔹 3. Dosing & Administration

Treatment must be initiated by a specialist experienced in oncology.

GIST and MRCC

• Dose: 50 mg orally once daily

• Schedule: 4 weeks ON, 2 weeks OFF (4/2 schedule)

• Cycle length: 6 weeks

Pancreatic NET

• Dose: 37.5 mg orally once daily

• Schedule: Continuous (no rest period)

Administration:

• Oral use

• May be taken with or without food

• If a dose is missed → do not double dose

🔹 4. Dose Modifications

• Adjust dose in 12.5 mg increments based on tolerability

• GIST/MRCC:

  • Maximum: 75 mg daily

  • Minimum: 25 mg daily

• pNET:

  • Maximum studied dose: 50 mg daily

CYP3A4 interactions:

• Strong CYP3A4 inhibitors → dose reduction may be required

• Strong CYP3A4 inducers → dose increase may be required

• Avoid where possible

🔹 5. Contraindications

• Hypersensitivity to sunitinib or excipients

• Pregnancy

• Breastfeeding

🔹 6. Monitoring Requirements

Baseline and ongoing:

• Blood pressure (frequent)

• Full blood count (each cycle)

• Liver function tests (ALT, AST, bilirubin)

• Thyroid function (baseline and periodically)

• Cardiac function (LVEF if risk factors present)

• ECG if QT prolongation risk

• Urinalysis (proteinuria)

• Blood glucose (especially in diabetics)

🔹 7. Common & Serious Adverse Effects

Very Common

• Fatigue

• Diarrhoea, nausea, vomiting

• Hypertension

• Hand-foot syndrome

• Stomatitis

• Skin discolouration

• Hypothyroidism

• Anorexia

Serious / Life-Threatening

• Heart failure, myocardial infarction

• QT prolongation, torsades de pointes

• Pulmonary embolism

• Severe haemorrhage

• Hepatic failure

• GI perforation

• Thrombotic microangiopathy

• Tumour lysis syndrome

• Stevens–Johnson syndrome

• Necrotising fasciitis

🔹 8. Use in Special Populations

• Elderly: No dose adjustment required

• Renal impairment: No starting dose adjustment required

• Hepatic impairment:

  • Mild–moderate: no adjustment

  • Severe: not studied

• Paediatrics: Safety and efficacy not established

• Pregnancy: Contraindicated

• Breastfeeding: Contraindicated

🔹 9. Fertility, Pregnancy & Lactation

• May impair fertility in males and females

• Effective contraception required during treatment and for 4 weeks after last dose

• Teratogenic in animal studies

• Excreted in breast milk → breastfeeding contraindicated

🔹 10. Duration of Use / When to Stop

Continue treatment until:

• Disease progression, or

• Unacceptable toxicity

Permanently discontinue if:

• Life-threatening cardiac toxicity

• Severe hepatotoxicity without recovery

• Thrombotic microangiopathy

• Stevens-Johnson syndrome

• Necrotising fasciitis

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2025/02/Sutent-12.5-25-50-mg-Capsules-LPD-PI-South-Africa.pdf