CISPLATIN

Basic Information

Cisplatin is a platinum-containing chemotherapy drug. Although the mechanism of action is not understood completely, cisplatin behaves similarly to a bi-functional alkylating agent by producing cross-links in DNA. Cisplatin is distributed widely in the liver, kidney and intestines and poorly into the central nervous system (CNS). Cisplatin is particularly nephrotoxic, and the kidneys excrete approximately 50% cisplatin in the first 24 to 48 hours. It is activated in the kidneys to produce a toxic metabolite to the proximal tubule cells.

Cisplatin is a mainstay chemotherapy drug to treat ovarian cancer in women. Although the majority of ovarian cancers respond initially to cisplatin, it appears that over time the tumours become resistant to platinum chemotherapy. There is research in human medicine attempting to identify other chemotherapy agents to enhance the effectiveness of cisplatin.

Dogs

Cisplatin is used to treat several different tumours in dogs. The most common ones include osteosarcoma, squamous cell carcinoma, bladder tumours, ovarian carcinoma, and mesotheliomas. It frequently is used to treat unresectable or widespread carcinomas and may be administered intravenously, intraperitoneally, or intralesionally.

Cisplatin has been shown to improve survival in dogs with osteosarcoma. In one study, the one-year survival for dogs with osteosarcoma that had undergone both tumour resection and cisplatin chemotherapy was 45-55%.

Horses

Cisplatin is used intralesionally to treat equine skin tumours such as sarcoids, spindle-cell tumours, squamous cell carcinoma, and melanoma. When used as an intra-lesional injection, cisplatin is either mixed with sterile sesame oil or delivered in a biodegradable, slow-release bead. In reports on intralesional use, systemic side effects were not noted, and local side effects resolved quickly.

A Biodegradable Matrix for Cisplatin to Treat Equine Skin Neoplasia, Marble, George P, Sullins, K.E., Marion DuPont Scott Equine Medical Center Department of Large-Animal Clinical Sciences.

Cisplatin Side-Effects in Dogs

The most common side effect is vomiting within six hours of treatment. This may be managed by pre-treatment with antiemetics such as butorphanol, dexamethasone, and metoclopramide. The degree of GI toxicity may be dose-related.

Nephrotoxicity frequently is a treatment-limiting side effect. Monitoring renal-concentrating ability, azotemia, and the presence of abnormal numbers of granular casts in urinary sediment may be useful. The risk of nephrotoxicity and ototoxicity may be decreased by slowing the infusion rate.

Another side-effect may be mild to moderate myelosuppression with a bimodal nadir at seven and 14 days. White blood cell (WBC) count should be monitored regularly in animals undergoing treatment.

Precautions

• Gloves and protective clothing should be worn when handling cisplatin.
• Cisplatin is nephrotoxic. It should not be used with extreme caution in dogs with decreased renal function. It should always be used with pre-and post-treatment saline diuresis. Cisplatin should be used with caution in dogs with urinary tumours. It should not be used if the serum creatinine is above the normal range. Small dogs may be at greater risk of developing nephrotoxicity than larger breed dogs.
• Dogs with pre-existing heart disease who cannot undergo fluid diuresis pre-treatment are not good candidates for cisplatin.
• Cisplatin should not be used in cats due to potential severe pulmonary toxicity.
• In laboratory animals, cisplatin was found to be embryotoxic and teratogenic. It should be used in pregnant animals only when the benefit of treatment outweighs the risks.
• Cisplatin should not come in contact with aluminum as it may cause the platinum to precipitate. Aluminum needles should be avoided. Discard any cisplatin with precipitate.

Drug Interactions

• Treatment with other potentially nephrotoxic drugs should be separated by two weeks.
• Cisplatin may decrease serum levels of phenytoin.

Overdose

There is a very narrow range between the therapeutic dose and the minimum lethal dose. Dosage calculations must be meticulously checked due to the toxicity of this drug.