Evaluation of toxicosis of liposome-encapsulated cis-bis-neodecanoato- trans-R,R-1,2-diaminocyclohexane platinum (II) in clinically normal cats

L. E. Fox, K. Toshach, M. Calderwood-Mays, A. R. Khokhar, P. Kubilis, Roman Perez-Soler, E. G. MacEwen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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. Animals - 10 healthy adult cats. Procedure - 8 cats were given a single dose of L-NDDP (at rates of 75, 100, 150, or 200 mg/m2), and 2 cats 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 myelosuppresion, 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 L-NDDP/m2). Conclusion - Cats can safely be given L-NDDP at potentially therapeutic dosages without inducing renal or pulmonary toxicoses. Clinical Relevance - 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.

Original languageEnglish (US)
Pages (from-to)257-263
Number of pages7
JournalAmerican Journal of Veterinary Research
Volume60
Issue number2
StatePublished - 1999
Externally publishedYes

Fingerprint

platinum
Liposomes
poisoning
Cats
cats
dosage
Lipidoses
Lethargy
cisplatin
Cisplatin
Vomiting
vomiting
Kidney
((1R,2R)-1,2-diaminocyclohexane)platinum(II)
Diphenhydramine
kidneys
Urinalysis
bis-neodecanoato-1,2-diaminocyclohexaneplatinum(II)
Liver
Transaminases

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Evaluation of toxicosis of liposome-encapsulated cis-bis-neodecanoato- trans-R,R-1,2-diaminocyclohexane platinum (II) in clinically normal cats. / Fox, L. E.; Toshach, K.; Calderwood-Mays, M.; Khokhar, A. R.; Kubilis, P.; Perez-Soler, Roman; MacEwen, E. G.

In: American Journal of Veterinary Research, Vol. 60, No. 2, 1999, p. 257-263.

Research output: Contribution to journalArticle

Fox, L. E. ; Toshach, K. ; Calderwood-Mays, M. ; Khokhar, A. R. ; Kubilis, P. ; Perez-Soler, Roman ; MacEwen, E. G. / Evaluation of toxicosis of liposome-encapsulated cis-bis-neodecanoato- trans-R,R-1,2-diaminocyclohexane platinum (II) in clinically normal cats. In: American Journal of Veterinary Research. 1999 ; Vol. 60, No. 2. pp. 257-263.
@article{78eb7005121f49bab82c4a462f063854,
title = "Evaluation of toxicosis of liposome-encapsulated cis-bis-neodecanoato- trans-R,R-1,2-diaminocyclohexane platinum (II) in clinically normal cats",
abstract = "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. Animals - 10 healthy adult cats. Procedure - 8 cats were given a single dose of L-NDDP (at rates of 75, 100, 150, or 200 mg/m2), and 2 cats 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 myelosuppresion, 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 L-NDDP/m2). Conclusion - Cats can safely be given L-NDDP at potentially therapeutic dosages without inducing renal or pulmonary toxicoses. Clinical Relevance - 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.",
author = "Fox, {L. E.} and K. Toshach and M. Calderwood-Mays and Khokhar, {A. R.} and P. Kubilis and Roman Perez-Soler and MacEwen, {E. G.}",
year = "1999",
language = "English (US)",
volume = "60",
pages = "257--263",
journal = "American Journal of Veterinary Research",
issn = "0002-9645",
publisher = "American Veterinary Medical Association",
number = "2",

}

TY - JOUR

T1 - Evaluation of toxicosis of liposome-encapsulated cis-bis-neodecanoato- trans-R,R-1,2-diaminocyclohexane platinum (II) in clinically normal cats

AU - Fox, L. E.

AU - Toshach, K.

AU - Calderwood-Mays, M.

AU - Khokhar, A. R.

AU - Kubilis, P.

AU - Perez-Soler, Roman

AU - MacEwen, E. G.

PY - 1999

Y1 - 1999

N2 - 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. Animals - 10 healthy adult cats. Procedure - 8 cats were given a single dose of L-NDDP (at rates of 75, 100, 150, or 200 mg/m2), and 2 cats 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 myelosuppresion, 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 L-NDDP/m2). Conclusion - Cats can safely be given L-NDDP at potentially therapeutic dosages without inducing renal or pulmonary toxicoses. Clinical Relevance - 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.

AB - 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. Animals - 10 healthy adult cats. Procedure - 8 cats were given a single dose of L-NDDP (at rates of 75, 100, 150, or 200 mg/m2), and 2 cats 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 myelosuppresion, 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 L-NDDP/m2). Conclusion - Cats can safely be given L-NDDP at potentially therapeutic dosages without inducing renal or pulmonary toxicoses. Clinical Relevance - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033032691&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033032691&partnerID=8YFLogxK

M3 - Article

C2 - 10048562

AN - SCOPUS:0033032691

VL - 60

SP - 257

EP - 263

JO - American Journal of Veterinary Research

JF - American Journal of Veterinary Research

SN - 0002-9645

IS - 2

ER -