Evaluation of toxicosis of liposome-encapsulated cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) in clinically normal cats.
OBJECTIVE
To determine adverse effects of single and multiple doses of liposome-encapsulated cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (L-NDDP) administered IV to healthy adult cats.


METHODS
10 healthy adult cats.


METHODS
8 cats were given a single dose of L-NDDP (at rates of 75, 100, 150, or 200 mg/m2), and 2 cats were given liposomal lipid (1,500 mg/m2). Six of the 10 cats were given doses of L-NDDP at the maximum tolerated dosage (100 mg/m2) or a lower dosage (75 mg of L-NDDP/m2) at 21-day intervals, for a total of 4 treatments. Hematologic and serum biochemical analyses, urinalyses, and physical examinations were used to monitor effects of L-NDDP.


RESULTS
All cats had transient pyrexia, lethargy, vomiting (1 to 3 times/24 h), inappetence, and an acute species-specific infusion reaction that was prevented by administration of atropine-diphenhydramine. Dose-limiting toxicosis was evident as a 10-day course of lethargy, intermittent vomiting, and diarrhea. In cats given multiple doses, dose-related thrombocytopenia, cumulative myelosuppression, transient increased hepatic transaminase activity, and mild to moderate hepatic hydropic degeneration and proximal renal tubular lipidosis in excess of lipidosis expected for this species were detected. Bone marrow hypoplasia was detected in some cats that received higher doses (cumulative dosages of 300 or 400 mg of L-NDDP/m2).


CONCLUSIONS
Cats can safely be given L-NDDP at potentially therapeutic dosages without inducing renal or pulmonary toxicoses.


CONCLUSIONS
Because L-NDDP has better tumoricidal activity than cisplatin (in vivo and in vitro) and is not cross resistant, it may be similarly or more efficacious than cisplatin in humans and dogs.
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0126, USA.
L E
LE
Fox
K
K
Toshach
M
M
Calderwood-Mays
A R
AR
Khokhar
P
P
Kubilis
R
R
Perez-Soler
E G
EG
MacEwen
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001774:Blood Chemical Analysis / Q000662:veterinary; D001831:Body Temperature; D002415:Cats / Q000502:physiology*; D004134:Dimyristoylphosphatidylcholine / Q000494:pharmacology; D004337:Drug Carriers; D005260:Female; D007202:Indicators and Reagents / Q000494:pharmacology; D008081:Liposomes; D008297:Male; D009504:Neutrophils / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000633:toxicity*; D010976:Platelet Count / Q000662:veterinary; D011897:Random Allocation; D018709:Statistics, Nonparametric; D016482:Urinalysis / Q000662:veterinary
D000970:Antineoplastic Agents; D004337:Drug Carriers; D007202:Indicators and Reagents; D008081:Liposomes; D009944:Organoplatinum Compounds; C054367:bis-neodecanoato-1,2-diaminocyclohexaneplatinum(II); D004134:Dimyristoylphosphatidylcholine