cisdiamminedichloroplatinumII

Cis-diamminedichloroplatinum(II), commonly known as cisplatin, is a platinum-based chemotherapy agent used to treat a variety of solid tumors. Its chemical formula is PtCl2(NH3)2, a square-planar complex with the two ammine (NH3) ligands and the two chloride ligands arranged in the cis configuration. In the body, the chloride ligands can be replaced by water molecules in a process called aquation, generating reactive species that interact with DNA.

Mechanism of action is primarily through covalent binding to DNA. The platinum complex forms crosslinks, especially 1,2-intrastrand crosslinks between adjacent guanine bases, which distort the DNA helix, interfere with replication and transcription, and activate cellular pathways leading to programmed cell death. Cisplatin is not a targeted therapy; its effects are broader and most pronounced in rapidly dividing cells.

Clinical use includes treatment of testicular cancer (often in combination regimens such as BEP: bleomycin, etoposide, and cisplatin), as well as ovarian, bladder, head and neck, cervical, and certain lung cancers. It is typically given as an intravenous infusion, with dosing and scheduling tailored to tumor type and patient factors. Cisplatin is eliminated primarily by the kidneys, so hydration and sometimes diuretic strategies are used to reduce nephrotoxicity. Common adverse effects include nephrotoxicity, ototoxicity (hearing loss), neurotoxicity, nausea and vomiting, and myelosuppression. Repeated cycles can lead to cumulative toxicity and may trigger hypersensitivity reactions. Resistance can arise through reduced drug uptake, increased detoxification, or enhanced DNA repair.

History notes: the anticancer activity of platinum compounds was discovered in the 1960s by Barnett Rosenberg and colleagues, with clinical approval of cisplatin occurring in the late 1970s. It remains a foundational agent in oncology, often used in combination with other therapies.