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Carboplatin

Carboplatin is an analogue of cisplatin.

It is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA cross-links and inhibition of DNA replication.

Carboplatin binds to protein and other compounds containing the SH group.

Cytotoxicity can occur at any stage of the cell cycle, but the cell is most vulnerable to the action of these drugs in the G1 and S phases.

Carboplatin has the same efficacy as cisplatin but a better toxicity profile.

Its main advantages over cisplatin include less nephrotoxicity and ototoxicity, absence of a need for extensive prehydration, and reduced likelihood of inducing nausea and vomiting; however, it is more likely to induce myelotoxicity.

Dosage modified according to formulas for glomerular filtration rates.

Can produce a wide spectrum of hypersensitivity reactions including erythroderma, tachycardia, chest tightness and wheezing, facial swelling, shortness of breath, hypotension and hypertension.

Causes hypersensitivity reactions usually after multiple courses of treatment and with a increased total dose.

More then 5 cycles of chemotherapy and/or more than 2500-7200 mg the drug administration significantly increases the incidence of hypersensitivity reactions.

Hypersensitivity reactions usually occur within the first 5-10 minutes of intravenous infusion.

Hypersensitivity reactions occur in 1% of patients receiving fewer than 5 courses of treatment, and up to 27% of patients receiving more than 7 treatments (Zanotti KM et al).

Skin tests for sensitivity is suggestive for patients after the sixth course of treatment.

Patients should be pretreated with corticosteroids and H1 and H2 antihistamines.

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