Carboplatin

Carboplatin is a second-generation platinum salt widely used in veterinary medicine, in both dogs and cats, for the treatment of many solid tumours (sarcomas and carcinomas). Carboplatin was introduced into clinical use with the aim of reducing the nephrotoxicity of cisplatin, while maintaining a similar antitumour efficacy.

CHEMICAL STRUCTURE AND PHARMACOKINETIC PROPERTIES

Carboplatin is formed of an atom of platinum complexed with two molecules of ammonia and two carboxylic esters. Compared to cisplatin, carboplatin is more stable (and, therefore, less reactive) and less toxic.

After intravenous administration, the plasma levels of carboplatin decrease in a biphasic manner following first-order kinetics. About 85% of the drug binds to plasma proteins within 24 hours of administration.

Carboplatin is excreted through the kidneys; about 70% of the drug is eliminated within 24 hours of administration, predominantly in an unmodified form.

MECHANISM OF ACTION

Within neoplastic cells, carboplatin forms reactive compounds that bind to the nucleophilic groups of DNA, causing inter-strand and intra-strand cross-links and DNA-protein bonds, inducing apoptosis and inhibiting cell growth. The action of carboplatin is independent of the phase of the cell cycle.

MECHANISM OF RESISTANCE

The main mechanisms of resistance of neoplastic cells to carboplatin are: altered transport and/or reduced accumulation of carboplatin within the cell, increased efflux and more efficient repair of the carboplatin-induced DNA damage.

CLINICAL INDICATIONS AND DOSE

Carboplatin is indicated for the treatment of osteosarcoma, melanoma, urothelial carcinoma, fibrosarcoma, squamous cell carcinoma, tonsillar carcinoma, mesothelioma, andcarcinomatosis.

Hydration is not necessary before administering carboplatin.

The dose in the dog is 260-300 mg/m_² intravenously every 3-4 weeks. The carboplatin must be diluted at a ratio of 1:10 with dextrose 5%. Carboplatin can also be administered directly into the relevant body cavity for the treatment of mesothelioma, carcinomatosis and sarcomatosis: the dose is 300 mg/m_² diluted in dextrose 5% at a ratio of 10 mg/ml; the solution thus obtained must be further diluted at a ratio of 1 ml/4.5 kg. An equivalent amount of physiological saline must be instilled before the administration of carboplatin.

The dose of carboplatin in the cat is 240 mg/m_² intravenously every 3-4 weeks. The drug must be diluted 1:10 with dextrose 5%.

TOXICITY

Carboplatin  can have side effects on the following organs and systems:

• bone marrow: cumulative, reversible bone marrow suppression (neutropenia, thrombocytopenia) related to renal clearance. Patients with impaired renal function are more susceptible to myelosuppression.
• gastrointestinal tract: mild toxicity (nausea, vomiting, loss of appetite).

Suggested readings

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