PLATAMINE

Indications

• Testicular cancer
• Ovarian cancer
• Bladder cancer
• Non-small cell lung cancer
• Head and neck cancers

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients.

Adults: Refer to the BNF for specific dosing information based on the type of cancer and patient characteristics.

Mechanism of action

Cisplatin works by attaching alkyl groups to DNA bases, leading to DNA fragmentation by repair enzymes, preventing DNA synthesis and RNA transcription. It also forms cross-links in the DNA, which inhibit the uncoiling necessary for replication, and induces mispairing of nucleotides, resulting in mutations.

Pharmacodynamics

As an antineoplastic agent, cisplatin disrupts DNA function by cross-linking guanine bases in the DNA double helix. This cross-linking directly inhibits DNA replication, causing cell death. It is classified as a cell cycle-nonspecific drug, meaning it can affect cells at any stage of the cell cycle.

Pharmacokinetics

Cisplatin is administered intravenously and distributed widely throughout the body. It is primarily excreted unchanged in the urine. The drug's half-life is approximately 30 minutes to 3 hours, but its effects on cancer cells can persist long after the drug is cleared from the bloodstream. Cisplatin's pharmacokinetics can be affected by factors such as renal function, as it is primarily eliminated by the kidneys.

Contra-indications

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

Adverse effects

• Nausea and vomiting
• Nephrotoxicity
• Neurotoxicity (peripheral neuropathy)
• Ototoxicity (hearing loss)
• Bone marrow suppression
• Electrolyte imbalances (e.g., hypomagnesemia, hypokalemia)

Interactions

• Other nephrotoxic agents (e.g., aminoglycosides, NSAIDs)
• Live vaccines
• Anticonvulsants (may alter metabolism of cisplatin)
• Anticoagulants (increased risk of bleeding)

Precautions

• Monitor renal function before and during treatment
• Prehydration and posthydration to minimize nephrotoxicity
• Caution in patients with pre-existing hearing loss
• Use with caution in patients with myelosuppression

Pregnancy

Cisplatin is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

Cisplatin is excreted in breast milk; breastfeeding is not recommended during treatment.

Storage

Store in a cool, dry place, protected from light. Keep out of reach of children.

Formulations

• Injection solution (e.g., cisplatin 1 mg/ml)

Mechanism of action

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.

Pharmacodynamics

Cisplatin is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.