5.7 Side effects of cisplatin

Cisplatin is a potent cytotoxic drug, which has limited targeting within the organism.

By its nature, it will bind to DNA within cells regardless of whether those cells are cancerous or not.

Fortunately, there are aspects of the biochemistry of cancer cells which render them more susceptible to damage from cisplatin, but there are still serious side effects associated with both DNA- and protein-bound platinum.

This limits the maximum dose of cisplatin to about 100 mg per day for up to five consecutive days.

The toxic side effects can be partially controlled by inhibiting the formation of Pt–protein complexes or by ‘rescuing’ platinum from these Pt–protein complexes.

A high concentration in the solution containing the drug helps to inhibit the formation of and RSH complexes, hence cisplatin is administered in a saline drip. This reduces kidney damage dramatically.

Rescue agents such as Structure 14 and 15 can be administered 3–4 h after cisplatin treatment.

Structure 14 (left) and 15 (right)

These agents displace platinum from sulfur-containing biomolecules but crucially do not affect Pt–DNA complexes.

A typical treatment regime will involve infusions of cisplatin followed by infusions of rescue agents, followed by a period of rest to allow normal cells which have been damaged by the cytotoxic drug to recover.

This cycle will typically be repeated several times to maximise the benefit of the treatment.