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  • Author or Editor: Roman Perez-Soler x
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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 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).

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. (Am J Vet Res 1999;60:257–263)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine clinical response and toxic effects of cis-bis-neodecanoato-trans-R,R-1,2- diaminocyclohexane platinum (II) (L-NDDP) administered IV at escalating doses to cats with oral squamous cell carcinoma (SCC).

Animals—18 cats with oral SCC.

Procedure—Cats that failed to respond to conventional treatment or had nonresectable tumors were included. Data included a CBC, serum biochemical analyses, urinalysis, cytologic examination of a fineneedle aspirate of enlarged lymph nodes, and thoracic and oral radiographs for clinical staging. A starting dose (75 to 100 mg/m2 of L-NDDP) was administered IV. At 21-day intervals, subsequent doses increased by the rate of 5 or 10 mg/m2. Response was evaluated every 21 days by tumor measurement and thoracic radiography. Quality of life was assessed by owners, using a performance status questionnaire.

Results—On average, cats received 2 treatments. Toxicoses included an intermittent, acute anaphylactoid- parasympathomimetic reaction, lethargy or sedation (≤ 24 hours), inappetence or signs of depression (≤ 72 hours), mild to moderate increase in hepatic enzyme activity, and melena. Pulmonary, renal, or hematopoietic abnormalities were not evident. Performance status surveys indicated normal behavior and grooming or decreased activity and self-care (19/20 assessments), ate well with or without assistance (15/20), and did not lose weight (15/20). Median survival time was 59.8 days (mean, 54.1 days).

Conclusions and Clinical Relevance—L-NDDP was ineffective for treatment of cats with oral SCC. None of the cats had a complete or partial remission. Acute toxicoses and poor therapeutic response limit therapeutic usefulness of L-NDDP in cats, unless dosage, frequency, and administration procedures can be improved. (Am J Vet Res 2000;61: 791–795)

Full access
in American Journal of Veterinary Research