Introduction
Oxaliplatin is a third-generation platinum-based chemotherapeutic agent that has revolutionized the treatment of colorectal cancer. As part of the alkylating agent class, it is distinguished from other platinum compounds by its 1,2-diaminocyclohexane (DACH) carrier ligand, which contributes to its unique efficacy profile and toxicity spectrum. First approved by the FDA in 2002, oxaliplatin has become a cornerstone in the management of gastrointestinal malignancies, particularly when combined with fluoropyrimidines.
Mechanism of Action
Oxaliplatin exerts its cytotoxic effects through formation of DNA adducts that ultimately trigger apoptotic cell death. The drug undergoes nonenzymatic conversion in physiological solutions to active derivatives that form both intrastrand and interstrand cross-links with DNA guanine bases. These platinum-DNA adducts create structural distortions that impede DNA replication and transcription. The DACH-platinum adducts are bulkier and more effective at bypassing DNA repair mechanisms compared to those formed by cisplatin or carboplatin, contributing to oxaliplatin's unique activity profile and reduced cross-resistance with other platinum agents.
Indications
- First-line treatment of advanced colorectal cancer in combination with infusional fluorouracil and leucovorin (FOLFOX regimen)
- Adjuvant treatment of stage III colon cancer following complete resection of primary tumor in combination with infusional fluorouracil and leucovorin
- Treatment of metastatic colorectal cancer in combination with capecitabine (XELOX regimen)
Dosage and Administration
Standard dosing: 85 mg/m² IV over 2-6 hours every 2 weeks in combination with fluorouracil/leucovorin Administration guidelines:- Administer via IV infusion using dextrose 5% solution only
- Do not use chloride-containing solutions (causes degradation)
- Infusion time: 2-6 hours (longer infusion may reduce acute neurotoxicity)
- Premedication with antiemetics recommended
- Renal impairment: Use with caution in CrCl <30 mL/min
- Hepatic impairment: No specific recommendations (use clinical judgment)
- Elderly patients: Monitor closely for increased toxicity
Pharmacokinetics
Absorption: Administered intravenously only; complete bioavailability Distribution: Extensive tissue distribution with volume of distribution of 440 L; highly protein bound (>90%) primarily to albumin and gamma-globulin Metabolism: Undergoes extensive non-enzymatic biotransformation to active and inactive compounds; not significantly metabolized by cytochrome P450 system Elimination: Primarily renal excretion (54% within 5 days); terminal half-life of 391 hours due to extensive tissue binding and slow releaseContraindications
- Hypersensitivity to oxaliplatin or other platinum compounds
- Pregnancy (Category D)
- Severe renal impairment (CrCl <30 mL/min) unless benefit outweighs risk
Warnings and Precautions
Neurotoxicity: Two distinct syndromes - acute (reversible cold-induced dysesthesia) and cumulative sensory neuropathy. May require dose reduction or discontinuation. Myelosuppression: Neutropenia and thrombocytopenia may occur; monitor blood counts regularly. Pulmonary toxicity: Interstitial lung disease reported; monitor for respiratory symptoms. Hepatotoxicity: Rare cases of hepatic vascular disorders reported. QT prolongation: May prolong QT interval; use with caution in patients with cardiac risk factors. Extravasation: Can cause local tissue damage; ensure proper IV placement.Drug Interactions
Nephrotoxic agents: Increased risk of renal toxicity with aminoglycosides, NSAIDs Anticoagulants: Possible increased bleeding risk with warfarin Live vaccines: Avoid concurrent administration CYP2C8 substrates: Potential interactions with paclitaxel, repaglinideAdverse Effects
Very common (>10%):- Peripheral sensory neuropathy (acute and chronic)
- Neutropenia, thrombocytopenia, anemia
- Nausea, vomiting, diarrhea
- Fatigue
- Elevated transaminases
- Stomatitis
- Anorexia
- Fever
- Allergic reactions
- Alopecia
- Anaphylaxis
- Pulmonary fibrosis
- Hemolytic uremic syndrome
- Posterior reversible encephalopathy syndrome (PRES)
Monitoring Parameters
Prior to each cycle:- Complete blood count with differential
- Comprehensive metabolic panel (renal and hepatic function)
- Physical and neurological examination
- Monitor for hypersensitivity reactions
- Observe for signs of extravasation
- Assessment of neuropathy symptoms
- Quality of life measures
- Response evaluation per RECIST criteria
Patient Education
- Report immediately any signs of allergic reaction (hives, difficulty breathing, swelling)
- Avoid cold temperatures and cold drinks/food for 3-5 days after treatment to reduce acute neurotoxicity
- Use gloves when handling cold objects
- Report any numbness, tingling, or pain in hands/feet
- Maintain adequate hydration
- Use reliable contraception during and for several months after treatment
- Report fever, chills, or signs of infection promptly
- Keep all scheduled follow-up appointments
References
1. Graham MA, et al. Clinical pharmacokinetics of oxaliplatin: a critical review. Clin Cancer Res. 2000;6(4):1205-1218. 2. NCCN Guidelines Version 2.2023 Colon Cancer. 3. Package Insert: Oxaliplatin Injection. FDA-approved labeling. 4. Gamelin E, et al. Clinical pharmacokinetics and pharmacodynamics of oxaliplatin. Clin Pharmacokinet. 2002;41(11):825-843. 5. André T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350(23):2343-2351. 6. Argyriou AA, et al. Oxaliplatin-induced peripheral neurotoxicity: clinical features, mechanisms, prevention and treatment. J Neurol. 2021;268(9):3269-3282.