Vincristine

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.