PLATIFIRST

Indications

• Advanced ovarian cancer
• Small cell lung cancer
• High-risk seminoma (stage I) testicular germ cell tumors (adjuvant treatment)
• Bladder cancer
• Cervical cancer
• Head and neck cancer

Dosage

Children: Paediatric dosing should be determined based on specific clinical guidelines and product literature, as this information is not directly provided in the BNF.

Adults: The dosage for adults varies based on the specific type of cancer being treated and should be determined by consulting product literature. Typically, it is administered by intravenous infusion.

Mechanism of action

Cisplatin exerts its anticancer effects primarily through the formation of DNA cross-links. The drug binds to DNA, forming interstrand and intrastrand cross-links that inhibit DNA replication and transcription, triggering cellular apoptosis. This mechanism is facilitated by the activation of cellular signaling pathways that respond to DNA damage, leading to cell cycle arrest and subsequent cell death.

Pharmacodynamics

Cisplatin is a cytotoxic agent that targets the DNA of cancer cells, causing significant damage that disrupts the normal processes of cell division and function. It is particularly effective against rapidly proliferating tumors. The drug's efficacy is influenced by factors such as the tumor type, stage, and cellular repair mechanisms.

Pharmacokinetics

Cisplatin has a variable pharmacokinetic profile, with a distribution half-life of approximately 30 minutes and a terminal half-life of about 48 to 100 hours. It is primarily eliminated through the kidneys, and renal function significantly affects its clearance. The drug is known to have dose-dependent nephrotoxicity, necessitating careful monitoring of renal function during treatment.

Contra-indications

• Hypersensitivity to cisplatin or any of its components
• Severe renal impairment
• Myelosuppression
• Pregnancy

Adverse effects

• Nausea
• Vomiting
• Alopecia
• Nephrotoxicity
• Ototoxicity
• Leukopenia
• Thrombocytopenia
• Anaphylactoid reactions
• Cardiac arrest (rare)
• Acute leukemia (rare)

Interactions

• Other nephrotoxic drugs (e.g., aminoglycosides, NSAIDs)
• Ototoxic agents (e.g., loop diuretics)
• Anticonvulsants (may require dosage adjustments)
• Radiation therapy (increased risk of toxicity)

Precautions

• Careful monitoring of renal function
• Hydration before and after administration to reduce nephrotoxicity
• Monitoring for signs of ototoxicity
• Caution in patients with pre-existing hearing impairment
• Use with caution in patients with cardiovascular disorders

Pregnancy

Cisplatin is classified as a Category D drug. It is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

Cisplatin is not recommended during breastfeeding due to potential excretion in breast milk and risk to the infant.

Storage

Store in a cool, dry place away from light. Store the solution in the refrigerator and protect from light.

Formulations

• Cisplatin 1 mg/ml solution for infusion
• Cisplatin 50 mg/50 ml solution for infusion