Drug Class: Multi-targeted tyrosine kinase inhibitor (TKI)
Mechanism of Action
- Inhibits multiple receptor tyrosine kinases including:
- VEGFR (vascular endothelial growth factor receptor) – inhibits angiogenesis
- PDGFR (platelet-derived growth factor receptor)
- c-KIT – important in some tumors like GIST
- Blocks tumor growth by:
- Reducing blood supply to tumors
- Inhibiting cancer cell proliferation and survival
Clinical Indications
- Renal Cell Carcinoma (RCC) – first-line for metastatic or advanced disease
- Gastrointestinal Stromal Tumor (GIST) – second-line after imatinib failure or intolerance
- Pancreatic Neuroendocrine Tumors (pNETs)
- Investigational use in other solid tumors (off-label)
Common Adverse Effects
- Fatigue, nausea, diarrhea
- Hand-foot syndrome (palmar-plantar erythrodysesthesia)
- Hypertension (due to VEGF inhibition)
- Hypothyroidism
- Mucositis, skin discoloration
- Myelosuppression (anemia, neutropenia, thrombocytopenia)
- Cardiotoxicity (rare but serious: ↓ LVEF or heart failure)
Clinical Considerations
- Given orally, once daily (typically 4 weeks on, 2 weeks off)
- Metabolized by CYP3A4 → watch for drug interactions
- Monitor:
- CBCs, LFTs, TSH, BP
- Cardiac function if risk factors or symptoms arise
- Resistance may develop with prolonged use, often via mutations or bypass signaling pathways