Class: Oral multikinase inhibitor (tyrosine kinase inhibitor, TKI).
Indications in sarcoma/related tumors:
- GIST (gastrointestinal stromal tumor): Approved for patients previously treated with imatinib and sunitinib.
- Also used in colorectal cancer and hepatocellular carcinoma (not sarcoma, but important overlap).
Mechanism of Action:
- Inhibits multiple kinases involved in angiogenesis (VEGFR1–3, TIE2), oncogenesis (KIT, RET, RAF), and tumor microenvironment (PDGFR, FGFR).
- Provides broad blockade of tumor growth signaling and angiogenesis.
Dosing (adult):
- 160 mg PO once daily (with a low-fat meal), for 3 weeks on / 1 week off (28-day cycle).
- Tablets = 40 mg → usually 4 tablets daily.
- Dose reductions: 120 mg → 80 mg if toxicity.
Key Toxicities (pharmacist needs to know):
- Hand-foot skin reaction (HFSR) (most distinctive, dose-limiting).
- Hepatotoxicity (can be severe/fatal, monitor closely).
- Hypertension.
- Fatigue, diarrhea, mucositis.
- Voice changes (dysphonia, common but benign).
- Rare: hemorrhage, cardiac ischemia.
Monitoring:
- LFTs: baseline, then every 2 weeks for first 2 months, monthly thereafter.
- BP: baseline and weekly early in therapy, then periodically.
- Skin/toxicity checks for HFSR — intervene early with emollients, urea-based creams, dose modifications.
- CBC, electrolytes as indicated.
- Watch for drug–drug interactions (CYP3A4 substrate; avoid strong inhibitors/inducers).
Pharmacist Pearls:
- Take with low-fat meal (high-fat meals ↑ exposure and toxicity).
- Counsel patients to report palmar-plantar skin changes, jaundice, dark urine, uncontrolled HTN.
- Dose interruptions and reductions are common for toxicity management.
- Hand-foot skin reaction prevention: prophylactic moisturizers, avoid friction/pressure, consider keratolytics.
- Patient adherence critical (oral therapy).
Take-home for BPS prep:
Regorafenib is an oral TKI used in GIST after imatinib & sunitinib. Pharmacists must monitor liver function, blood pressure, and skin toxicity (HFSR), and reinforce adherence and food instructions (low-fat meals).
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