VEGF Tyrosine Kinase Inhibitors (TKIs)
Class / Mechanism
- Small-molecule tyrosine kinase inhibitors that block vascular endothelial growth factor (VEGF) receptor signaling.
- Inhibit angiogenesis, depriving tumors of blood supply → limits tumor growth and metastasis.
Common VEGF TKIs and Indications
| Drug (Brand) | Primary Targets | Indications (Oncology) | Typical Dose | Key Toxicities / Monitoring |
|---|---|---|---|---|
| Sunitinib (Sutent) | VEGFR1-3, PDGFR, KIT, FLT3 | RCC, GIST (after imatinib), pancreatic neuroendocrine tumors | 50 mg PO daily, 4 wk on/2 wk off | Hypertension, hand–foot syndrome, myelosuppression, hepatotoxicity, hypothyroidism; monitor CBC, LFTs, BP |
| Sorafenib (Nexavar) | VEGFR2-3, PDGFR, RAF | RCC, HCC, thyroid carcinoma | 400 mg PO BID | Hypertension, rash, diarrhea, hand–foot syndrome, hepatotoxicity; monitor BP, LFTs |
| Pazopanib (Votrient) | VEGFR1-3, PDGFR, KIT | RCC, soft tissue sarcoma | 800 mg PO daily | Hypertension, hepatotoxicity, diarrhea, hair depigmentation; monitor BP, LFTs |
| Axitinib (Inlyta) | VEGFR1-3 | RCC (second-line) | 5 mg PO BID | Hypertension, fatigue, diarrhea; monitor BP, renal function |
| Cabozantinib (Cabometyx, Cometriq) | VEGFR2, MET, AXL | RCC, HCC, medullary thyroid carcinoma | 60 mg PO daily (RCC) | Hypertension, diarrhea, hand–foot syndrome, hepatotoxicity; monitor BP, LFTs |
| Lenvatinib (Lenvima) | VEGFR1-3, FGFR1-4, PDGFR, RET, KIT | RCC (with everolimus), HCC, thyroid carcinoma | 24 mg PO daily (thyroid) | Hypertension, proteinuria, diarrhea, fatigue, hepatotoxicity; monitor BP, urine protein, LFTs |
Class Toxicities / Monitoring
- Hypertension → monitor BP regularly; treat promptly.
- Proteinuria → monitor urine protein/creatinine.
- Hepatotoxicity → monitor LFTs.
- Hand–foot syndrome / rash → supportive care, dose adjustments.
- Diarrhea, fatigue, weight loss → supportive measures.
- QT prolongation (some agents, e.g., sunitinib, cabozantinib) → ECG monitoring if risk present.
Pharmacist Pearls
- Oral administration → adherence counseling critical.
- CYP3A4 metabolism → watch for drug–drug interactions.
- Dose adjustments often required for toxicity (hepatic impairment, severe hypertension, hand–foot syndrome).
- Educate patients on BP monitoring, recognizing bleeding, and managing GI side effects.
- Often used in RCC, HCC, thyroid cancer, sometimes in combination with immunotherapy.
Summary:
- VEGF TKIs are anti-angiogenic oral agents used across multiple solid tumors.
- Class toxicities are hypertension, hepatotoxicity, proteinuria, diarrhea, and hand–foot syndrome.
- Monitoring and patient counseling are critical to safe and effective use.