Cisplatin

Cisplatin, chemically cis-diamminedichloroplatinum(II), is a platinum-based chemotherapeutic agent used to treat multiple solid tumors. After administration, the compound forms reactive platinum species that bind DNA and create intra- and interstrand cross-links, most notably at adjacent guanine residues. These DNA adducts disrupt replication and transcription, triggering apoptosis in rapidly dividing cancer cells.

Clinical use: It plays a central role in germ cell tumors, particularly testicular cancer, and is also employed for ovarian, bladder, cervical, head and neck, lung, and gastrointestinal cancers. Cisplatin is frequently given in combination regimens (for example, BEP for testicular cancer) and can be used with radiotherapy in selected settings.

Administration and safety: Cisplatin is given intravenously, with hydration and, in some regimens, electrolyte supplementation to protect renal function. Acute toxicity includes nausea and vomiting; long-term toxicities include nephrotoxicity, ototoxicity, and peripheral neuropathy. Electrolyte disturbances (notably magnesium and potassium) may occur; myelosuppression is variable. Dose adjustments are based on renal function and treatment goals.

Pharmacology and history: The drug is largely excreted by the kidneys and forms DNA adducts that underlie its cytotoxic effect. Resistance mechanisms include reduced uptake, increased DNA repair, and detoxification by intracellular thiols. Cisplatin was discovered in the 1960s by Rosenberg and colleagues and was approved for medical use in 1978. It remains a foundational platinum-based chemotherapy, with newer agents offering different toxicity and efficacy profiles.