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

• Colorectal cancer – adjuvant (Stage III) and metastatic (often with 5-FU/leucovorin in FOLFOX)
• Off-label: gastric, pancreatic, biliary tract cancers

Adult Dosing (common regimens)

• FOLFOX: 85 mg/m² IV over 2 hrs day 1 q2 weeks
• CAPOX: 130 mg/m² IV over 2 hrs day 1 q3 weeks (Always with 5-FU/LV or capecitabine)

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

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