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Carboplatin belongs to the class of platinum-containing antineoplastic agents, which also includes cisplatin and oxaliplatin. Carboplatin, a second generation analog of cisplatin, has cytotoxic activity similar to cisplatin. Once inside the cell, carboplatin is hydroxylated by water to form the active compound, then it covalently binds to DNA at two sites, forming interstrand and intrastrand cross-links. This irreversible binding results in the inhibition of DNA replication. Carboplatin is a cell cycle non-specific agent with increased activity during the S-phase. It causes cell cycle arrest in the G2-phase; then induces cellular apoptosis.
Carboplatin is administered primarily through IV infusion. Unlike cisplatin, it has minimal protein binding and distributes well into ascites, pleural fluid, liver, kidney, skin and tumor tissues. Carboplatin has minimal hepatic metabolism; rather, it undergoes spontaneous hydrolysis to become active. It is primarily excreted by the kidneys via tubular filtration. The exposure to carboplatin is well characterized by its AUC, which is associated with its antineoplastic activity as well as toxicity. Carboplatin is much less toxic than cisplatin, but its dose-limiting toxicity is myelosuppression (especially thrombocytopenia). An AUC of 4 to 7 has manageable myelosuppressive effects with desirable efficacy against malignant cancers. Since carboplatin is less nephrotoxic, neurotoxic and emetogenic than cisplatin, it can be an ideal agent for dose-intensive and/or combination chemotherapies.
Carboplatin was introduced in 1981 as a favorable alternative to cisplatin for the treatment of many solid tumors. Carboplatin is FDA approved for the initial or palliative (previously treated with cisplatin) treatment of advanced ovarian tumors when combined with other approved chemotherapy agents. Carboplatin is also used in a variety of malignancies such as ovarian cancer, bladder cancer, metastatic breast cancer, cervical cancer, esophageal cancer, head and neck cancer, lymphoma, lung cancer, unknown primary adenocarcinoma and testicular cancer.
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- Calvert Formula
- Dosing in Obese Patients: 10-11
- New FDA Recommendations on Capping Parameters: 12
- Dosing Guidelines