Pharmacological Class
- Vinca alkaloid (plant alkaloid, antimicrotubule agent)
Mechanism of Action
- Binds to tubulin, inhibiting microtubule polymerization.
- Prevents spindle formation during metaphase → cell cycle arrest in M phase.
- Leads to apoptosis of rapidly dividing cancer cells.
Indications (common uses in oncology/hematology)
- ALL (acute lymphoblastic leukemia) – cornerstone of induction regimens
- Hodgkin & Non-Hodgkin lymphomas
- Wilms’ tumor, neuroblastoma, rhabdomyosarcoma (pediatrics)
- Part of many combination regimens (e.g., CHOP for NHL, MOPP for HL, etc.)
Dosing
- Adults: 1.4 mg/m² IV once weekly (max single dose = 2 mg, to limit neurotoxicity)
- Pediatrics: 1.5–2 mg/m² IV once weekly (dose capped at 2 mg)
Never administer intrathecally → fatal neurotoxicity
Dose Adjustments
- Hepatic impairment (reduce dose by 50% if bilirubin > 1.5 mg/dL, by 75% if > 3 mg/dL)
- Renal impairment: No major adjustment needed
Toxicities / Side Effects
- Dose-limiting:
- Neurotoxicity (peripheral neuropathy, constipation, paralytic ileus, cranial nerve palsies, jaw pain, foot drop)
- Other toxicities:
-
- Mild myelosuppression (much less than vinblastine)
- SIADH (hyponatremia)
- Alopecia
- Vesicant (causes tissue necrosis if extravasated)
Monitoring
- Neurologic exam (baseline & ongoing)
- Bowel function (watch for constipation/ileus)
- Serum sodium (SIADH risk)
- CBC (though less myelosuppressive than other vincas)
- LFTs (dose adjustment if impaired)
Clinical Pearls
- Cap dose at 2 mg (even in larger BSA) to prevent neurotoxicity
- IV only → fatal if given intrathecally (must label syringes clearly)
- Avoid with strong CYP3A4 inhibitors (azole antifungals, macrolides) → ↑ neurotoxicity risk
- Often combined with steroids (e.g., dexamethasone, prednisone) and other chemo in pediatric protocols
Summary for practice:
Vincristine is a vinca alkaloid, M-phase specific, with neurotoxicity as the dose-limiting effect. Always cap at 2 mg, never give intrathecally, and monitor neurologic status + bowel function closely.