cisplatin

A platinum-based antineoplastic medication used in chemotherapy given intravenously to treat cancers, such as sarcomas, carcinomas (e.g. small cell lung cancer, squamous cell carcinoma of the head and neck and ovarian cancer), lymphomas, bladder cancer, cervical cancer, germ cell tumors (e.g. testicular cancer), mesothelioma, brain tumors, and neuroblastoma.
Use during pregnancy can cause harm to the developing fetus.

(Side effects)
Common:
• bone marrow suppression
• neurotoxicity: Nerve damage. Ototoxicity, usually restricted to one ear, but possibly total irreversible hearing loss. Visual perception disorder.
• nephrotoxicity: Kidney damage.
• nausea, vomiting
Serious:
• numbness
• trouble walking
• allergic reactions
• electrolyte disturbance: Hypomagnesaemia, hypokalaemia, and hypocalcaemia.
• heart disease
• hemolytic anemia: Hemolysis occurs by an antibody reacting with a cisplatin-red-cell membrane.

It works in part by binding to DNA and inhibiting its replication, which kills the fastest proliferating cells, which in theory are cancerous.
Subsequent to formation of [PtCl(guanine-DNA)(NH3)2]+, crosslinking can occur via displacement of the other chloride, typically by another guanine. Cisplatin crosslinks DNA in several different ways, interfering with cell division by mitosis. The damaged DNA elicits DNA repair mechanisms, which in turn activate apoptosis when repair proves impossible.

The majority of cancer patients will eventually relapse with cisplatin-resistant disease.
Many mechanisms of cisplatin resistance have been proposed, including changes in cellular uptake and efflux of the drug, increased detoxification of the drug, inhibition of apoptosis and increased DNA repair.
Paclitaxel is also a chemotherapy medication, that may be useful in the treatment of cisplatin-resistant cancer.

(Comparisons)
• cisplatin: Used in chemotherapy
• transplatin: The trans-stereoisomer of cisplatin, trans-[PtCl2(NH3)2]. It does not exhibit a comparably useful pharmacological effect.