cisplatin
Summary
Cisplatin is a platinum-based alkylating-like chemotherapy agent that crosslinks DNA, causing apoptosis in rapidly dividing cancer cells. It is used to treat testicular, ovarian, bladder, and lung cancers. Its major dose-limiting toxicities are nephrotoxicity and ototoxicity.
Detail
Mechanism: Cisplatin forms intrastrand and interstrand DNA crosslinks (primarily at guanine N7 positions), which prevents DNA replication and transcription, ultimately triggering apoptosis. It is cell-cycle nonspecific.
Clinical uses: Testicular cancer (curative in combination regimens, e.g., BEP - bleomycin, etoposide, cisplatin), ovarian cancer, bladder cancer, non-small cell and small cell lung cancer, head and neck cancers, and cervical cancer.
Toxicities (high-yield for boards): - Nephrotoxicity: Dose-limiting; causes acute tubular necrosis, particularly affecting the proximal and distal tubules. Prevented/reduced with aggressive IV hydration (saline diuresis) before and after administration. - Ototoxicity: Irreversible hearing loss, especially high-frequency; caused by damage to cochlear hair cells. - Peripheral neuropathy (dose-dependent, cumulative). - Severe nausea/vomiting (highly emetogenic - requires prophylactic antiemetics like 5-HT3 antagonists + NK1 antagonists + dexamethasone). - Electrolyte wasting: Hypomagnesemia, hypokalemia, hypocalcemia due to renal tubular damage. - Myelosuppression (less severe than other alkylating agents).
Resistance mechanisms: Increased DNA repair (nucleotide excision repair), decreased drug uptake, increased glutathione/metallothionein (which inactivate cisplatin), and decreased apoptotic signaling.
Comparison: Carboplatin has similar mechanism but less nephrotoxicity/ototoxicity, more myelosuppression (thrombocytopenia). Oxaliplatin causes peripheral neuropathy exacerbated by cold exposure and is used mainly in colorectal cancer.
Mnemonic: Cisplatin toxicity - remember 'OH, No CRAB!' variations, but key triad to remember: Nephrotoxicity, Ototoxicity, Neurotoxicity ('the 3 N's plus O').
Sources
- First Aid for the USMLE Step 1
- Katzung's Basic and Clinical Pharmacology
- Goodman & Gilman's Pharmacological Basis of Therapeutics
- UpToDate - Cisplatin: Drug information
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.