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  • Author or Editor: Ilene D. Kurzman x
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Abstract

Objective—To determine the acute and short-term adverse effects of a liposome-encapsulated form of cisplatin at increasing dosages of up to twice the known maximally tolerated dose (MTD) of unencapsulated cisplatin in clinically normal dogs.

Animals—4 healthy 2.5-year-old sexually intact female hound-type dogs.

Procedure—4 dosages (70, 100, 125, and 150 mg/m2) were evaluated, and the 4 dogs received a total of 9 infusions (1 to 3 infusions/dog). Dogs were monitored to detect changes in clinical and clinicopathologic status. Evaluations consisting of a physical examination, CBC, serum biochemical analysis, and urinalysis were performed before and 7 and 21 days after each infusion.

Results—Acute anaphylactic-like reactions to liposome- encapsulated cisplatin were common but clinically manageable. Nephrotoxicosis and substantial myelosuppression, toxic effects commonly associated with unencapsulated cisplatin, were not observed in dogs treated with liposome-encapsulated cisplatin at dosages equivalent to twice the known MTD of unencapsulated cisplatin.

Conclusions and Clinical Relevance—Liposome-encapsulated cisplatin can be safely administered to clinically normal dogs at dosages of up to 150 mg/m2 without the need for concurrent hydration protocols. This was a necessary prerequisite to enable phase I clinical trials in dogs with naturally developing cancers that could theoretically benefit from escalation in the dosage of cisplatin. Determination of an MTD, cumulative and long-term toxic effects, and efficacy can now be conducted in the context of phase I trials in tumorbearing dogs. (Am J Vet Res 2004;65:1474–1478)

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in American Journal of Veterinary Research

Abstract

Objective—To characterize demographics and clinical signs and evaluate outcomes of treatments in cats with transitional cell carcinoma (TCC) of the urinary bladder.

Design—Retrospective case series.

Animals—20 cats with TCC.

Procedures—Medical records of 20 cats with a bladder mass identified as a TCC that were examined at 2 veterinary institutions between 1990 and 2004 were evaluated. Signalment, treatments, and outcome were assessed.

Results—Breeds included domestic short hair (n = 14), long hair (2), and medium hair (2) cats, Siamese (1), and Abyssinian (1). All cats had been neutered at an early age (< 1 year old; 13 neutered males and 7 spayed females). The median age at diagnosis of TCC was 15.2 years. The trigone region was affected in 9 cats. Treatments included piroxicam administration, chemotherapy, or surgery as single interventions or in combination; 6 cats were not treated. At the time of diagnosis, 3 cats had pulmonary metastasis and 1 cat had metastasis to local lymph nodes. Median survival time for all 20 cats was 261 days. Nearly all deaths were attributable to progressive disease in the urinary tract. Five cats were lost to follow-up.

Conclusions and Clinical Relevance—In cats, TCC of the urinary bladder appears to be a rare and aggressive disease that is more prevalent in male cats and frequently develops at sites distant from the trigone (unlike TCC in dogs). Nevertheless, initial clinical signs of TCC in cats in this study were similar to those reported for affected dogs.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate the safety and efficacy of a vaccine containing plasmid DNA with an insert encoding human tyrosinase (ie, huTyr vaccine) as adjunctive treatment for oral malignant melanoma (MM) in dogs.

Animals—111 dogs (58 prospectively enrolled in a multicenter clinical trial and 53 historical controls) with stage II or III oral MM (modified World Health Organization staging scale, I to IV) in which locoregional disease control was achieved.

Procedures—58 dogs received an initial series of 4 injections of huTyr vaccine (102 μg of DNA/injection) administered transdermally by use of a needle-free IM vaccination device. Dogs were monitored for adverse reactions. Surviving dogs received booster injections at 6-month intervals thereafter. Survival time for vaccinates was compared with that of historical control dogs via Kaplan-Meier survival analysis for the outcome of death.

Results—Kaplan-Meier analysis of survival time until death attributable to MM was determined to be significantly improved for dogs that received the huTyr vaccine, compared with that of historical controls. However, median survival time could not be determined for vaccinates because < 50% died of MM before the end of the observation period. No systemic reactions requiring veterinary intervention were associated with vaccination. Local reactions were primarily limited to acute wheal or hematoma formation, mild signs of pain at the injection site, and postvaccination bruising.

Conclusions and Clinical Relevance—Results support the safety and efficacy of the huTyr DNA vaccine in dogs as adjunctive treatment for oral MM.

Impact for Human Medicine—Response to DNA vaccination in dogs with oral MM may be useful in development of plasmid DNA vaccination protocols for human patients with similar disease.

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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)

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in American Journal of Veterinary Research