Cisplatin

Cisplatin forms inter- and intrastrand DNA cross-links to inhibit DNA synthesis. The pharmacokinetics are best described by a three-compartment model, with an a-half-life of 20 minutes, a B-half-life of 48 to 70 minutes, and a terminal half-life of 24 hours. Ninety percent of the drug is removed by the kidney by glomerular filtration and tubular secretion. Cisplatin has shown clinical activity in the treatment of numerous tumor types, from head and neck cancers to anal cancer, including many types of lymphoma and carcinoma of unknown primary. Cisplatin is highly emetogenic, even when low doses are given daily for 5 days, and causes delayed nausea and vomiting as well; patients require aggressive antiemetic regimens for both delayed and acute emesis. Significant nephrotoxicity and electrolyte abnormalities can occur if inadequate hy-

dration occurs. Ototoxicity, which manifests as a high-frequency hearing loss, and a glove-and-stocking neuropathy may limit therapy.

Carboplatin

While carboplatin has the same mechanism of action as cisplatin, it has a much less toxic side-effect profile than cisplatin. The pharmacokinetics of carboplatin are best described by a two-compartment model, with an a-half-life of 90 minutes and a terminal half-life of 180 minutes. Carboplatin is eliminated almost entirely by the kidney by glomerular filtration and tubular secretion. Many chemotherapy regimens dose carboplatin based on an area under the curve (AUC), which is referred to as the Calvert equation. According to the Calvert equation, the dose in milligrams = (CrCl + 25) x

AUC desired. Carboplatin has shown clinical activity in the treatment of ovarian, lung, breast, testicular, esophageal, and head and neck cancers, as well as lymphomas. Thrombocytopenia, nausea and vomiting, and hypersensitivity reactions are side effects.

Oxaliplatin

The pharmacokinetics of oxaliplatin are best described by a three-compartment model, with an a-half-life of 0.28 hours, a B-half-life of 16.3 hours, and a terminal half-life of

273 hours. Oxaliplatin has shown clinical activity in the treatment of colorectal cancer. Oxaliplatin, while similar in action to cisplatin and carboplatin, causes a cold-induced neuropathy. Patients should be counseled to avoid cold beverages, to use gloves to remove items from the freezer, and to wear protective clothing in cold climates for the first week after treatment. A glove-and-stocking neuropathy also occurs with long-term dosing. Hypersensitivity reactions and moderate nausea and vomiting are also side effects.

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