Cisplatin

Platinum-containing antineoplastic agent Alkylating-like agent

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IV 60-70 mg/m² Every 3-4 weeks Duration: Up to 4-6 cycles depending on response and toxicity
Notes: Must be administered with saline diuresis (0.9% NaCl at 18.3 ml/kg/hr for 4 hours before and after) to reduce nephrotoxicity. Premedicate with antiemetics (e.g., maropitant).
Cat IV Not recommended; if used, 10-20 mg/m² with aggressive fluid support Every 3-4 weeks Duration: Limited; monitor for severe toxicity
Notes: Cats are extremely sensitive to cisplatin; fatal pulmonary edema has been reported. Use only if no alternative.
Horse IV or intralesional IV: 50-60 mg/m²; Intralesional: 1 mg/cm³ of tumor IV: every 3 weeks; Intralesional: weekly for 3-4 treatments Duration: As needed
Notes: IV administration requires saline diuresis. Intralesional injection is used for equine sarcoids and squamous cell carcinoma.

Clinical Indications & Species Uses

General Indications
  • Antineoplastic agent for various solid tumors
Dog (Canine)
  • Osteosarcoma (adjuvant therapy after amputation)
  • Lymphoma (rescue therapy)
  • Mammary carcinoma
  • Squamous cell carcinoma
  • Transitional cell carcinoma of the bladder
  • Mesothelioma
  • Various sarcomas
Horse (Equine)
  • Squamous cell carcinoma (intralesional or systemic)
  • Lymphoma (rarely used)

Pharmacology & Mechanism of Action

Drug Class: Platinum-containing antineoplastic agent | Pharmacological Group: Alkylating-like agent

Mechanism of Action: Cisplatin is a platinum coordination complex that exerts its cytotoxic effects by forming intrastrand and interstrand crosslinks with DNA. The platinum atom binds covalently to the N7 position of guanine and adenine bases, causing DNA damage that leads to inhibition of DNA replication and transcription. This triggers cell cycle arrest (primarily at G2 phase) and apoptosis. The drug is cell cycle non-specific but is most effective in rapidly dividing cells.

Pharmacodynamics: Cisplatin exhibits dose-dependent cytotoxicity against a wide range of tumors. It is most effective in solid tumors, particularly those of epithelial origin. The drug's activity is enhanced in hypoxic conditions and is schedule-dependent, with fractionated dosing often improving efficacy and reducing toxicity. Resistance can develop through decreased drug accumulation, increased DNA repair, and increased glutathione conjugation.

⚡ Pharmacokinetics Summary

Absorption: Cisplatin is not absorbed orally; it is administered intravenously. After IV administration, peak plasma concentrations are achieved immediately.
Distribution: Cisplatin rapidly distributes into tissues, with highest concentrations in the kidneys, liver, and skin. It penetrates poorly into the central nervous system due to its hydrophilic nature. Protein binding is extensive, with over 90% bound to plasma proteins, primarily albumin and transferrin.
Metabolism: Cisplatin undergoes non-enzymatic biotransformation. The chloride ligands are displaced by water molecules (aquation) to form reactive species that bind to DNA and proteins. It is also conjugated with glutathione and metallothionein, which are pathways of detoxification.
Excretion: Cisplatin is primarily eliminated by renal excretion. The parent drug and its metabolites are excreted in urine via glomerular filtration and tubular secretion. Biliary excretion is minimal. Renal clearance is high, and the drug accumulates in the kidneys, leading to dose-limiting nephrotoxicity.
Half-Life: The terminal half-life in dogs is approximately 30-70 minutes for the free drug, but the total platinum half-life is much longer (several days) due to tissue binding and slow release.
Bioavailability: Not orally bioavailable; must be administered parenterally.
Protein Binding: >90% bound to plasma proteins

Available Formulations & Strengths

Injectable Solution 1 mg/mL (as aqueous solution) (IV)
Lyophilized Powder for Injection 10 mg, 50 mg vials (IV)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to cisplatin or other platinum compounds
  • Severe renal impairment (creatinine > 2.0 mg/dL or azotemia)
  • Severe myelosuppression (neutrophils < 2000/µL, platelets < 100,000/µL)
  • Pregnancy (teratogenic)
  • Lactating animals (excreted in milk)
  • Cats (relative contraindication due to high risk of fatal pulmonary toxicity)
Warnings & Clinical Precautions:
  • Nephrotoxicity is dose-limiting; ensure adequate hydration and saline diuresis before and after administration.
  • Myelosuppression is common; monitor CBC regularly.
  • Severe emesis is common; premedicate with antiemetics.
  • Ototoxicity and peripheral neuropathy may occur.
  • Cisplatin is a vesicant; extravasation can cause severe tissue necrosis.
  • Use with caution in animals with pre-existing hearing loss or neuropathy.
  • Wear protective gloves and handle in a biological safety cabinet.
  • Do not use aluminum needles or syringes; cisplatin reacts with aluminum.
  • In food animals, do not use due to prolonged withdrawal times and toxicity.

Adverse Effects & Reactions

Common:

  • Nausea and vomiting
  • Nephrotoxicity (increased BUN/creatinine, proteinuria)
  • Myelosuppression (leukopenia, thrombocytopenia)
  • Anorexia
  • Diarrhea

Serious / Severe:

  • Acute renal failure
  • Severe myelosuppression with sepsis
  • Anaphylaxis
  • Pulmonary edema (especially in cats)
  • Hepatotoxicity
  • Neurotoxicity (seizures, ataxia)

Rare:

  • Ototoxicity (deafness)
  • Cardiotoxicity
  • Electrolyte imbalances (hypomagnesemia, hypocalcemia)
  • Secondary malignancies

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Aminoglycoside antibiotics (e.g., gentamicin) Additive nephrotoxicity and ototoxicity High
Nonsteroidal anti-inflammatory drugs (NSAIDs) Increased risk of nephrotoxicity High
Loop diuretics (e.g., furosemide) Additive ototoxicity and nephrotoxicity Moderate
Other nephrotoxic drugs (e.g., amphotericin B) Increased renal toxicity High
Myelosuppressive agents (e.g., doxorubicin) Additive bone marrow suppression Moderate
Anticonvulsants (e.g., phenytoin) Decreased phenytoin absorption Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe and prolonged myelosuppression
  • Acute renal failure
  • Intractable vomiting
  • Seizures
  • Deafness
  • Electrolyte disturbances

Emergency Treatment Protocol: There is no specific antidote. Treatment is supportive and symptomatic. Maintain hydration with IV fluids (0.9% NaCl) to enhance renal excretion and minimize nephrotoxicity. Consider hemodialysis or peritoneal dialysis for severe renal failure. Administer antiemetics (e.g., maropitant, ondansetron). Provide broad-spectrum antibiotics if neutropenic. Monitor CBC, renal function, and electrolytes closely. Consider granulocyte colony-stimulating factor (G-CSF) for severe neutropenia.

Food Animal Withdrawal Times

Cisplatin is not approved for use in food animals. Use in food animals is prohibited due to the potential for prolonged tissue residues and severe toxicity. No withdrawal times are established.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (15-30°C) and protect from light.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Do not refrigerate or freeze. Reconstituted solutions are stable for 24 hours at room temperature. Protect from light and avoid contact with aluminum.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary species; approved for human use.

Extra-Label (Off-Label) Use: In the US, cisplatin is not FDA-approved for veterinary use but is used extra-label under the Animal Medicinal Drug Use Clarification Act (AMDUCA). Extra-label use is permitted only by or on the order of a licensed veterinarian within a valid veterinarian-client-patient relationship. Use in food animals is prohibited.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Cisplatin is a potent antineoplastic agent used primarily in dogs for osteosarcoma and other solid tumors. Its use is limited by significant nephrotoxicity and emesis, which can be mitigated with saline diuresis and antiemetic premedication. It is absolutely contraindicated in cats due to the risk of fatal pulmonary edema. In horses, intralesional administration is preferred for local tumors. Due to its toxicity and handling hazards, cisplatin should only be administered by experienced veterinary oncologists in a controlled setting. Always monitor renal function and CBC before each dose. Do not use in food animals. Consider alternative platinum agents (e.g., carboplatin) in cats or when nephrotoxicity is a concern.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)