Sunitinib — Drug Monograph

Brand names: Sutent

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Oral multitargeted receptor tyrosine kinase inhibitor (TKI) that simultaneously inhibits VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β, KIT (CD117), FLT3, CSF1R (colony-stimulating factor-1 receptor), and RET. Blocks tumor angiogenesis (VEGFR/PDGFR) and directly inhibits tumor cell proliferation (KIT in GIST, FLT3 in AML).

FDA Indications

• Advanced renal cell carcinoma (RCC) — FDA approved January 2006 (SUN1107: PFS 11 vs 5 months vs IFN-alfa)
• Gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib — FDA approved January 2006
• Progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs) — FDA approved May 2011 (A6181111: PFS HR 0.42)

Common Side Effects

• Fatigue
• Diarrhea
• Nausea and vomiting
• Mucositis/stomatitis
• Hand-foot syndrome
• Skin discoloration (yellow/orange — benign, from SU12662 metabolite)
• Hypertension
• Hypothyroidism
• Myelosuppression (neutropenia, thrombocytopenia)
• Hair color changes (depigmentation)

Clinical Pearl

Yellow or orange skin and hair discoloration occurs in up to 30% of patients due to the quinoxaline metabolite SU12662 and is completely benign — proactively warn patients to prevent alarm or unnecessary discontinuation. Hypothyroidism is surprisingly common (~36%) and often under-recognized; routine TSH monitoring each cycle with prompt levothyroxine replacement significantly improves fatigue and quality of life. VEGFR-TKI hand-foot skin reaction (HFSR) targets hyperkeratotic friction points…

Related Therapies & Mechanisms

• Axitinib (Inlyta) — Tyrosine Kinase Inhibitor · RCC
• Cabozantinib (Cabometyx) — Tyrosine Kinase Inhibitor · RCC
• Lenvatinib (Lenvima) — Tyrosine Kinase Inhibitor · RCC
• Pazopanib (Votrient) — Tyrosine Kinase Inhibitor · RCC