PRECLINICAL EVALUATION OF A STERICALLY STABILIZED LIPOSOME-ENCAPSULATED CISPLATIN IN CLINICALLY NORMAL CATS

Objective-To evaluate the effects of administration of a sterically st abilized liposome-encapsulated cisplatin (SSL-CDDP) to cats. Animals-4 clinically normal cats. Procedure-2 of the cats were given multiple I V injections of SSL-CDDP at a dosage of 70 mg of free CDDP equivalent/ m(2) of body surface area at 3-week intervals. The other 2 cats receiv ed single IV injections of identical liposome preparations not contain ing CDDP. Vital signs; appetite; attitude; hematologic, serum biochemi cal, and urinalysis findings; and thoracic radiographic views were eva luated at predetermined intervals. Results-Sterically stabilized lipos ome-encapsulated cisplatin was well tolerated by all cats. The only si gnificant alterations in measured variables were an increase in serum cholesterol concentration 2 days after injection, and repeatable pyrex ia in the cats receiving SSL-CDDP that began 10 to 12 hours after inje ction acid continued for 18 hours, peaking at 40.5 to 41 C. Alteration s in rectal temperature were not significant in cats receiving empty l iposome vehicle. Conclusions-SSL-CDDP appears to be safe to administer to cats at a dosage of 70 mg of free CDDP equivalent/m(2), a CDDP dos e known to be therapeutic in dogs. Pyrexia, although marked, appears t o be a short-term and well tolerated side effect. Clinical Relevance-S SL-CDDP appears to abrogate the uniformly fatal side effects associate d with administration of tumoricidal quantities of free CDDP to cats. This new formulation should allow investigation of the antitumor prope rties of CDDP against spontaneously arising neoplasms in cats.