carboplatin
Summary
Carboplatin is a second-generation platinum-based chemotherapeutic agent that causes DNA crosslinking (intrastrand and interstrand), leading to inhibition of DNA replication and transcription, ultimately triggering apoptosis in rapidly dividing cells. It is used to treat ovarian, lung, and other solid tumors, and is favored over cisplatin due to a more favorable toxicity profile.
Detail
Carboplatin is an alkylating-like platinum compound (though not a true alkylating agent) that forms platinum-DNA adducts, causing intrastrand and interstrand crosslinks between purine bases. This crosslinking distorts the DNA helix, preventing proper replication and transcription, and activates apoptotic pathways in cancer cells—effects that are cell-cycle nonspecific.
Mechanism: Similar to cisplatin, carboplatin undergoes aquation (hydrolysis) intracellularly to form reactive platinum species that bind to N7 of guanine and adenine, forming DNA adducts and crosslinks.
Clinical uses: Ovarian cancer, non-small cell and small cell lung cancer, head and neck cancers, bladder cancer, and endometrial cancer. Often used in combination regimens (e.g., carboplatin + paclitaxel for ovarian and lung cancers).
Comparison to cisplatin: Carboplatin has a bulkier bidentate dicarboxylate (cyclobutane-dicarboxylate, CBDCA) leaving group compared to cisplatin's chloride ligands, making it more stable and less reactive, requiring higher doses but resulting in reduced nephrotoxicity, ototoxicity, and neurotoxicity compared to cisplatin. However, carboplatin causes more significant myelosuppression, particularly thrombocytopenia.
Toxicity profile (high-yield for boards): - Myelosuppression (dose-limiting toxicity): thrombocytopenia > neutropenia > anemia - Less nephrotoxic than cisplatin (though can still occur, especially with renal impairment) - Less ototoxic and neurotoxic than cisplatin - Nausea/vomiting (less severe than cisplatin) - Hypersensitivity reactions (can occur with repeated cycles)
Dosing: Often calculated using the Calvert formula based on renal function (GFR) and target AUC (area under curve), reflecting its primary renal excretion.
Resistance mechanisms: Increased DNA repair (nucleotide excision repair), decreased drug uptake, increased glutathione/metallothionein (which bind and inactivate platinum), and mutations in mismatch repair pathways.
Monitoring: CBC (for myelosuppression), renal function tests, and signs of hypersensitivity.
Sources
- Katzung's Basic & Clinical Pharmacology
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- First Aid for the USMLE Step 1
- UpToDate: Carboplatin drug information
- DeVita's Cancer: Principles & Practice of Oncology
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.