Oxaliplatin is a platinum-based chemotherapy drug used primarily in the treatment of colorectal cancer. It belongs to the class of alkylating agents and works by interfering with the DNA replication process of cancer cells, ultimately causing cell death.

1. Mechanism of Action

Oxaliplatin, like other platinum compounds, forms covalent bonds with DNA, resulting in the formation of DNA adducts. This leads to cross-linking of DNA strands, preventing DNA replication and transcription. The DNA damage activates cellular pathways that lead to apoptosis (programmed cell death). Oxaliplatin specifically binds to purine bases in DNA, disrupting cellular processes and leading to tumor cell death.

2. Indications

• Colorectal cancer: It is commonly used in combination with other chemotherapeutic agents (like fluorouracil and leucovorin) to treat both metastatic colorectal cancer and adjuvantly in patients after surgery to reduce the risk of recurrence.
• Other cancer types: Investigational use in cancers like gastric, pancreatic, and ovarian cancers, though its primary approval is for colorectal malignancies.

3. Dosage and Administration

• Route: Intravenous (IV) infusion.
• Adult Dosage:
  • For Colorectal Cancer (Metastatic):
    • Oxaliplatin is typically given every 2 weeks.
    • Standard dosing: 85 mg/m² IV over 2 hours, every 2 weeks, in combination with fluorouracil and leucovorin.
  • Adjuvant Therapy:
    • Dose may be adjusted based on patient tolerance and the specific treatment regimen.
• Pediatric Dosage: Dosing in pediatric patients is based on body surface area (BSA) and is generally lower than adult doses. Specific guidelines and clinical judgment should be used.

Note: Always adjust doses based on patient condition, liver function, and any side effects.

4. Contraindications

• Hypersensitivity to oxaliplatin or any component of the formulation.
• Severe or persistent peripheral neuropathy (this may be exacerbated by oxaliplatin).

5. Warnings and Precautions

• Neuropathy: Peripheral neuropathy (tingling, numbness, or pain in extremities) is a common side effect, particularly with cold exposure. It may be acute (reversible) or chronic (potentially irreversible).
• Myelosuppression: Monitor blood counts closely for neutropenia, anemia, and thrombocytopenia.
• Hematologic Toxicity: Risk of severe bone marrow suppression. Regular monitoring of CBC is necessary.
• Gastrointestinal Toxicity: Nausea, vomiting, and diarrhea are common. Pre-emptive antiemetic therapy may be required.
• Pregnancy Category: Category D (Risk to fetus, should not be used during pregnancy unless absolutely necessary).

6. Side Effects

• Common:
  • Nausea and vomiting
  • Peripheral neuropathy (cold-induced or persistent)
  • Fatigue
  • Diarrhea
  • Anemia, neutropenia, thrombocytopenia
• Serious:
  • Severe allergic reactions (e.g., anaphylaxis)
  • Sepsis
  • Severe neutropenia or thrombocytopenia leading to infection risk
  • Life-threatening gastrointestinal reactions, including bleeding and perforation

7. Drug Interactions

• Fluoroquinolones: Increased risk of severe or prolonged neutropenia when used in combination with antibiotics such as ciprofloxacin.
• Phenytoin: There is a potential for interaction with anticonvulsants, requiring careful monitoring of drug levels.

8. Pharmacokinetics

• Absorption: Not absorbed orally (parenteral administration required).
• Distribution: Oxaliplatin is widely distributed in the body, with a volume of distribution of approximately 16–23 L.
• Metabolism: Oxaliplatin undergoes non-enzymatic hydrolysis to form active metabolites, which then interact with DNA. There is limited liver metabolism.
• Excretion: Approximately 10% of oxaliplatin is excreted in the urine, with the rest undergoing metabolic degradation.

9. Storage

• Store in the refrigerator (2–8°C, 36–46°F).
• Protect from light and avoid freezing.
• Once reconstituted, the solution should be used within 24 hours.