Preclinical evaluation of a sterically stabilized liposome-encapsulated cisplatin in clinically normal cats

Douglas H. Thamm From the Department of Medical Sciences, School of Veterinary Medicine (Thamm, Vail), and the Comprehensive Cancer Center (Vail), University of Wisconsin-Madison, 2015 Linden Dr W, Madison, WI 53706.

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David M. Vail From the Department of Medical Sciences, School of Veterinary Medicine (Thamm, Vail), and the Comprehensive Cancer Center (Vail), University of Wisconsin-Madison, 2015 Linden Dr W, Madison, WI 53706.

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Abstract

Objective

To evaluate the effects of administration of a sterically stabilized liposome-encapsulated cisplatin (SSL-CDDP) to cats.

Animals

4 clinically normal cats.

Procedure

2 of the cats were given multiple IV injections of SSL-CDDP at a dosage of 70 mg of free CDDP equivalent/m2 of body surface area at 3-week intervals. The other 2 cats received single IV injections of identical liposome preparations not containing CDDP. Vital signs; appetite; attitude; hematologic, serum biochemical, and urinalysis findings; and thoracic radiographic views were evaluated at predetermined intervals.

Results

Sterically stabilized liposome-encapsulated cisplatin was well tolerated by all cats. The only significant alterations in measured variables were an increase in serum cholesterol concentration 2 days after injection, and repeatable pyrexia in the cats receiving SSL-CDDP that began 10 to 12 hours after injection and continued for 18 hours, peaking at 40.5 to 41 C. Alterations in rectal temperature were not significant in cats receiving empty liposome vehicle.

Conclusions

SSL-CDDP appears to be safe to administer to cats at a dosage of 70 mg of free CDDP equivalent/m2, a CDDP dose known to be therapeutic in dogs. Pyrexia, although marked, appears to be a short-term and well tolerated side effect.

Clinical Relevance

SSL-CDDP appears to abrogate the uniformly fatal side effects associated with administration of tumoricidal quantities of free CDDP to cats. This new formulation should allow investigation of the antitumor properties of CDDP against spontaneously arising neoplasms in cats. (Am J Vet Res 1998;59:286–289)

Abstract

Objective

To evaluate the effects of administration of a sterically stabilized liposome-encapsulated cisplatin (SSL-CDDP) to cats.

Animals

4 clinically normal cats.

Procedure

2 of the cats were given multiple IV injections of SSL-CDDP at a dosage of 70 mg of free CDDP equivalent/m2 of body surface area at 3-week intervals. The other 2 cats received single IV injections of identical liposome preparations not containing CDDP. Vital signs; appetite; attitude; hematologic, serum biochemical, and urinalysis findings; and thoracic radiographic views were evaluated at predetermined intervals.

Results

Sterically stabilized liposome-encapsulated cisplatin was well tolerated by all cats. The only significant alterations in measured variables were an increase in serum cholesterol concentration 2 days after injection, and repeatable pyrexia in the cats receiving SSL-CDDP that began 10 to 12 hours after injection and continued for 18 hours, peaking at 40.5 to 41 C. Alterations in rectal temperature were not significant in cats receiving empty liposome vehicle.

Conclusions

SSL-CDDP appears to be safe to administer to cats at a dosage of 70 mg of free CDDP equivalent/m2, a CDDP dose known to be therapeutic in dogs. Pyrexia, although marked, appears to be a short-term and well tolerated side effect.

Clinical Relevance

SSL-CDDP appears to abrogate the uniformly fatal side effects associated with administration of tumoricidal quantities of free CDDP to cats. This new formulation should allow investigation of the antitumor properties of CDDP against spontaneously arising neoplasms in cats. (Am J Vet Res 1998;59:286–289)

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