Platinum analogues

Cis-platinum and various platinum analogues are among the most effective and common drugs in chemotherapy and are often combined with other cytostatic drugs.

For example, the complex cis-[Pt(NH3)2Cl2] = cisplatin is characterized by the binding of 2 chlorine ligands and 2 NH3 groups to the central platinum atom. After diffusion into the cell, the chlorine ligands are replaced by water, resulting in a reactive aquo-complex which acts similar to a bifunctional alkylane-type. This leads to an intrastrand crosslinking of the DNA. Here the aquo-complex reacts preferentially with the N7-atom of guanine and adenine. In addition, platinum analogues can cause point mutations and inhibit repair enzymes and telomerase activity. Cisplatin and carboplatin are applied i.v. and mainly eliminated renally. Cisplatin accumulates preferentially in the liver, kidneys and gonads.

The very strong and desired anti-apoptotic effect of the platinum analogues is accompanied by strong side effects that may limit therapy.

Platinumloga listed according to clinical significance:

• cisplatin
• Carboplatinum
• Oxaliplatin
• Satraplatin

testicular cancer, colon cancer, cervical cancer, ovarian cancer, bladder cancer. Further indications are esophageal and bronchial carcinomas as well as squamous cell carcinomas of the neck.

The main symptoms are nausea, anaemia and kidney damage (carboplatin). Hearing damage (ototoxicity) and nerve damage up to polyneuropathy are rarely reversible. With carboplatin, nephrotoxicity is the dose-limiting side effect. With carbobplatin, myelosuppression is the dose-limiting side effect. In the case of oxaliplatin, inflammation of the mucous membranes (mucositis) and sensory neuropathies of the hands and feet are the most common. Oxaliplatin is not nephrotoxic.

1. Dasari S et al (2014) Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 740:364-78
2. Hardie ME et al (2016) Cisplatin Analogues with an Increased Interaction with DNA: Prospects for Therapy. Curr Pharm Des 22: 6645-6664.
3. Oun R et al (2017) Cisplatin induced arrhythmia; electrolyte imbalance or disturbance of the SA node? Eur J Pharmacol 811:125-128.