Carboplatin, cisplatin, and oxaliplatin are heavy metal complex-es that contain platinum. Because their action resembles that of a bifunctional alkylating drug, they are referred to as alkylating-likedrugs.
The distribution and metabolism of carboplatin aren’t defined clearly. After I.V. administration, carboplatin is eliminated primari-ly by the kidneys. The elimination of carboplatin is biphasic. It has an initial half-life of 1 to 2 hours and a terminal half-life of 21⁄2 to 6 hours. In patients with decreased renal function, the ter-minal half-life of carboplatin may last from 30 to 300 hours.Oxali-platin is 70% to 90% bound to plasma proteins, and the protein-binding increases over time. It’s widely distributed into most body tissues and is eliminated in phases.
When administered intrapleurally (into the pleural space around the lung) or intraperitoneally (into the peritoneum), cisplatin may exhibit significant systemic absorption. Highly protein bound, cis-platin reaches high concentrations in the kidneys, liver, intestines, and testes but has poor central nervous system (CNS) penetra-tion. The drug undergoes some liver metabolism, followed by ex-cretion through the kidney.
Platinum is detectable in tissue for at least 4 months after admin-istration.
Like alkylating drugs, carboplatin, cisplatin, and oxaliplatin are cell cycle–nonspecific and inhibit DNA synthesis. They act likebifunctional alkylating drugs by cross-linking strands of DNA andinhibiting DNA synthesis.
These alkylating-like drugs are used in the treatment of severalcancers.
• Carboplatin is used primarily to treat ovarian and lung cancer.
• Cisplatin is prescribed to treat bladder and metastatic ovarian
• Cisplatin is the drug of choice to treat metastatic testicular cancers.
• Cisplatin may also be used to treat head, neck, and lung cancer (although these indications are clinically accepted, they’re currently unlabeled uses).
• Oxaliplatin is used in combination with other agents to treatcolorectal cancer.
Alkylating-like drugs interact with a few other drugs:
• When carboplatin, oxaliplatin, or cisplatin is administered with an aminoglycoside, the risk of toxicity to the kidney increases
• Carboplatin or cisplatin taken with bumetanide, ethacrynic acid,or furosemide increases the risk of ototoxicity (damaging the organs of hearing and balance)gans of hearing and balance).
• Cisplatin may reduce serum phenytoin levels. (See Adverse reactions to alkylating-like drugs.)