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Cisplatin for Veterinary Use
by Barbara Forney, VMD
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 into the liver, kidney and intestines and is distributed poorly into the central nervous system (CNS). Cisplatin is particularly nephrotoxic and approximately 50% of cisplatin is excreted by the kidneys in the first 24 to 48 hours. It is activated in the kidneys to produce a metabolite that is toxic 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 tumors become resistant to platinum chemotherapy. There is research in human medicine attempting to identify other chemotherapy agents to enhance the effectiveness of cisplatin.
Cisplatin is used to treat a number of different tumors in dogs. The most common ones include osteosarcoma, squamous cell carcinoma, bladder tumors, ovarian carcinoma and mesotheliomas. It frequently is used to treat non-resectable or widespread carcinomas and may be administered intravenously, intraperitoneally or intra-lesionally.
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 tumor resection and cisplatin chemotherapy was 45-55%.
Cisplatin is used intra-lesionally to treat equine skin tumors such as sarcoids, spindle cell tumors, 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 intra-lesional use, systemic side effects were not noted and local side effects resolved quickly.
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 the treatment limiting side effect. Monitoring renal concentrating ability, azotemia and 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.
- Gloves and protective clothing should be worn when handling cisplatin.
- Cisplatin is nephrotoxic. It should not be used or should be used with extreme caution, in dogs with decreased renal function. It always should be used with pre- and post- treatment saline diuresis. Cisplatin should be used with caution in dogs with urinary tumors. It should not be used if the serum creatinine is above normal range. Small dogs may be at greater risk to develop nephrotoxicity than larger breed dogs.
- Dogs with pre-existing heart disease that are unable to 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 embryo toxic and teratogenic. It should be used in pregnant animals only when the benefit of treatment clearly 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.
- Treatment with other potentially nephrotoxic drugs should be separated by two weeks.
- Cisplatin may decrease serum levels of phenytoin.
There is a very narrow range between the therapeutic dose and the minimum lethal dose. Dosage calculations need to be meticulously checked due to the toxicity of this drug.
About the Author
Dr. Barbara Forney is a veterinary practitioner in Chester County, Pennsylvania. She has a master's degree in animal science from the University of Delaware and graduated from the University of Pennsylvania School of Veterinary Medicine in 1982.
She began to develop her interest in client education and medical writing in 1997. Recent publications include portions of The Pill Book Guide to Medication for Your Dog and Cat, and most recently Understanding Equine Medications published by the Bloodhorse.
You can purchase books by Dr. Forney at www.exclusivelyequine.com
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