Oxaliplatin

Drug Class: Platinum-based alkylating-like agent

Mechanism of Action Forms platinum–DNA adducts (both inter- and intrastrand crosslinks), disrupting DNA replication and transcription → apoptosis. Unlike cisplatin, the diaminocyclohexane (DACH) carrier ligand may help overcome cisplatin resistance.

Indications

Adult Dosing (common regimens)

Renal Dose Adjustment

  • CrCl ≥30 mL/min → no adjustment
  • CrCl <30 mL/min → avoid or reduce to ~65 mg/m² (per label/clinical judgment)

Hepatic Dose Adjustment: No standard adjustment unless severe impairment; use caution if significant bilirubin elevation.

Pharmacokinetics

  • No CYP metabolism; nonenzymatic biotransformation to active derivatives
  • Excretion: ~50% renal
  • t½ terminal phase: 200–250 h (platinum bound to proteins)

Key Toxicities:

  • Peripheral neuropathy:
    • Acute (within hours–days; cold-triggered, reversible)
    • Cumulative (chronic, dose-limiting, may be irreversible)
  • Myelosuppression (neutropenia, thrombocytopenia)
  • Nausea/vomiting (moderate; often requires prophylaxis)
  • Hypersensitivity reactions (may occur after multiple cycles)</li><li>Rare: pulmonary fibrosis, RPLS (posterior reversible encephalopathy syndrome)

Neuropathy Counseling & Management

  • Acute: avoid cold drinks/exposure for ~5 days post-infusion (use gloves, scarf for cold weather)
  • Chronic: dose-reduce, space out cycles, or discontinue if functionally limiting

Drug Interactions

No major CYP interactions; avoid concurrent nephrotoxins; may enhance neurotoxicity with other neurotoxic agents.

Monitoring

  • CBC before each cycle
  • Renal function
  • Neurological exam for neuropathy progression
  • Signs of hypersensitivity

Clinical Pearls

  • Does not require mannitol or hyperhydration like cisplatin
  • Administer before 5-FU/leucovorin in FOLFOX
  • Infuse in D5W (degrades in chloride-containing solutions)
  • Acute neuropathy is often reversible within days; chronic neuropathy risk ↑ >850–1000 mg/m² cumulative dose