Alkylating-like drugs

Alkylating-like drugs

Carboplatin, cisplatin, and oxaliplatin are heavy metal complexes that contain platinum. Because their action resembles that of a bifunctional alkylating drug, they are referred to as alkylating-like drugs.

Pharmacokinetics

The distribution and metabolism of carboplatin aren’t defined clearly. After I.V. administration, carboplatin is eliminated primarily 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 2½ to 6 hours. In patients with decreased renal function, the terminal half-life of carboplatin may last from 30 to 300 hours.Oxaliplatin 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.

Into the lungs and peritoneum

 

When administered intrapleurally (into the pleural space around the lung) or intraperitoneally (into the peritoneum), cisplatin may exhibit significant systemic absorption. Highly protein bound, cisplatin reaches high concentrations in the kidneys, liver, intestines, and testes but has poor central nervous system (CNS) penetration. The drug undergoes some liver metabolism, followed by excretion through the kidney.

 

Going platinum

Platinum is detectable in tissue for at least 4 months after administration.

Pharmacodynamics

Like alkylating drugs, carboplatin, cisplatin, and oxaliplatin are cell cycle’nonspecific and inhibit DNA synthesis. They act like bifunctional alkylating drugs by cross-linking strands of DNA and inhibiting DNA synthesis.

Pharmacotherapeutics

These alkylating-like drugs are used in the treatment of several cancers.

• Carboplatin is used primarily to treat ovarian and lung cancer.
• Cisplatin is prescribed to treat bladder and metastatic ovarian cancer.
• 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 treat colorectal cancer.

Drug interactions

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).
• Cisplatin may reduce serum phenytoin levels. 

Warning!

Adverse reactions to alkylating-like drugs

Alkylating-like drugs produce many of the same adverse reactions as the alkylating drugs.

• Carboplatin can produce bone marrow suppression.
• Kidney toxicity may occur with cisplatin, usually after multiple courses of therapy. Carboplatin is less toxic to the kidneys.
• Cisplatin produces marked nausea and vomiting. With long-term cisplatin therapy, neurotoxicity can occur. Neurotoxicity is less common with carboplatin.
• Tinnitus and hearing loss may occur with cisplatin and, less commonly, with carboplatin.
• Oxaliplatin may cause anaphylaxis, anemia, or increased risk of bleeding or infection.