Cisplatin is used in chemotherapy to treat different types of cancer: testicular, ovarian, gallbladder, head and neck, small cell lung cancer and non-small cell lung cancer, breast, cervical and other epithelial carcinomas. In addition, cisplatin is used for the treatment of various lymphomas, neuroblastomas, sarcomas, multiple myeloma, melanoma and mesothelioma.
Mechanism of action
Cisplatin is a toxic platinum-based antineoplastic compound. The mechanism by which cisplatin kills cells is mediated by inhibition of DNA synthesis through the production of crosslinks between DNA strands. On the other hand, to a lesser extent, RNA and protein synthesis are inhibited.
Other mechanisms of cisplatin cytotoxicity include mitochondrial damage, decreased ATPase activity, and altered cellular transport mechanisms. Cytotoxicity increases with exposure during the S phase of the cell cycle, a phase that begins with nuclear DNA replication and ends when the DNA has been duplicated. Cisplatin causes cell cycle arrest in the G2 phase (phase where the cell prepares for cell division) and then induces programmed cell death or apoptosis.
Cisplatin has immunosuppressive, radiosensitizing and antibacterial properties.
Hypersensitivity to cisplatin or other platinum-based compounds.
Cisplatin should be avoided in patients with renal insufficiency, dehydration, myelosuppression, hearing impairment or neuropathy caused by cisplatin.
As discussed above, cisplatin is a truly toxic antineoplastic agent, for this reason a wide variety of side effects can occur during treatment:
- Infections, sepsis, leukopenia, thrombocytopenia and dose-dependent anemia.
- Peripheral neuropathy, hearing loss, vertigo.
- Cardiac arrhythmia
- Pneumonia and respiratory failure
- Anorexia, nausea, vomiting, diarrhea
- Liver failure
Renal and neuropathic toxicities of cisplatin are due to the interaction of activated cisplatin with critical renal and nervous system tissues. Cisplatin is associated with proximal and distal tubule damage due to cisplatin activation in renal tubules.
Neurotoxicity due to cisplatin may be due to cisplatin-induced damage to Schwann cells, which make up the myelin sheath surrounding nerves.