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in Journal of the American Veterinary Medical Association

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

Summary

Pretreatment characteristics of 138 dogs with malignant lymphoma were analyzed to determine prognostic factors associated with outcome (ie, complete response rate, time to relapse after complete response, survival time). Dogs were all treated for 10 weeks, using a standard induction chemotherapy protocol, and were then given asparaginase weekly. Once the disease became progressive, second-line chemotherapy was instituted.

Age, sex, weight, clinical stage, performance grade, immunophenotype, and malignancy grade assigned according to the National Cancer Institute's Working Formulation were not associated with complete response rate. However, malignancy grade assigned according to the Kiel classification was found to be associated with complete response rate; dogs with high-grade malignancies had a significantly higher complete response rate than did dogs with low-grade malignancies.

By means of multivariate analysis, clinical stage and immunophenotype were found to be prognostic factors for time to relapse (among dogs that had had a complete response) and survival time. In addition, malignancy grade assigned according to the Kiel classification was found to be a prognostic factor for time to relapse; whereas, malignancy grade assigned according to the Working Formulation was determined to be a prognostic factor for survival time.

Free access
in Journal of the American Veterinary Medical Association

SUMMARY

The effects of treatment with l-thyroxine (1 mg/m2 of body surface/d, po, for 8 weeks) on the thyroxine (T4) and triiodothyronine (T3) responses to thyrotropin (tsh) and thyrotropin-releasing hormone (trh) administration were determined in 10 euthyroid Beagles; 4 other dogs acted as controls. The tsh response test was performed before treatment and at weeks 2, 4, and 8 of treatment in all dogs and at 2 and 4 weeks after cessation of treatment in 6 dogs. The trh response test was performed before treatment and at week 6 of treatment in all dogs and at 5 weeks after cessation of treatment in 6 dogs.

Suppression of the T3 response to tsh was evident at treatment week 2, whereas the T4 response was suppressed at week 4 and remained suppressed for the duration of the study. Four weeks after l-thyroxine treatment was stopped, T3 response to tsh had returned to pretreatment values. Four weeks after stopping treatment, T4 and T3 responses to tsh in 2 dogs were within the hypothyroid range. The T4 response to trh was completely suppressed after 6 weeks of thyroxine treatment, but returned to pretreatment values by 5 weeks after cessation of treatment. Suppression of thyroid and pituitary function is evident after administration of a replacement dose of l-thyroxine to euthyroid dogs.

Free access
in American Journal of Veterinary Research

SUMMARY

To determine the effects of long-term thyroxine treatment, histomorphometric analysis was performed on the pituitary and thyroid glands of healthy dogs, dogs treated for 9 weeks with a replacement dose of l-thyroxine, and dogs at 6 weeks after cessation of thyroxine treatment. In treated dogs, the volume density of thyrotropes decreased during thyroxine treatment and increased 6 weeks after cessation of treatment, compared with thyrotropes of healthy nontreated dogs. The activity of the thyroid gland was decreased in dogs during thyroxine treatment, as evidenced by decreases in epithelial volume density, epithelial height, and follicular area, and increase in colloid volume density, compared with thyroid gland activity in nontreated dogs. After cessation of thyroxine treatment, the thyroid gland had decreased colloid area, follicular area, and epithelial volume density, and increased interstitial volume density, compared with the thyroid gland of healthy nontreated dogs. Thyroxine treatment resulted in suppression of pituitary thyrotropes and thyroid follicular activity.

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

Summary

Long-term follow-up information pertaining to 162 dogs with appendicular osteosarcoma treated by amputation alone was collected from 17 veterinary institutions. The majority (72.5%) of dogs died or were euthanatized because of problems documented to be related to metastases. The first clinically apparent sites of metastasis were the lungs (60.8% of total), the skeleton (5.2%), or both (4.6%). A Kaplan-Meier survivorship distribution was plotted on the basis of available survival time data in all 162 dogs. The mean and median survival times were estimated to be 19.8 and 19.2 weeks, respectively, and the 1- and 2-year survival rates were estimated to be 11.5 and 2.0% respectively.

Statistically significant relationships were not found between survival time and reporting institution, gender, site of primary tumor, whether the primary tumor was proximally or distally located, whether the primary tumor was located in the forelimb or hind limb, whether presurgical biopsy was performed, and whether death was tumor related. A significant (P < 0.01) quadratic relationship was found between age and survival time. Survival time was longest in dogs 7 to 10 years old and was shorter in older and younger dogs.

Free access
in Journal of the American Veterinary Medical Association