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  • Author or Editor: Kenneth M. Rassnick x
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Abstract

OBJECTIVE To determine histologic and clinical factors associated with survival time in dogs with stage II splenic hemangiosarcoma treated by splenectomy and a chemotherapy protocol in which an anthracycline was alternated with lomustine.

DESIGN Retrospective case series.

ANIMALS 30 dogs with stage II splenic hemangiosarcoma.

PROCEDURES Medical records of 3 facilities were reviewed to identify dogs treated for stage II splenic hemangiosarcoma between June 2011 and October 2014. Information collected included signalment, disease staging data, whether anemia was present, date of splenectomy, chemotherapy protocol, adverse effects, and date of death or last follow-up. Histologic slides were reviewed and scored by pathologists. Associations between variables of interest and survival data were evaluated statistically.

RESULTS Median survival time for all dogs was 158 days (range, 55 to 560 days), and the 1-year survival rate was 16%. On multivariate analysis, only the histologically determined mitotic score was significantly associated with survival time. The median survival time of 292 days for dogs with a mitotic score of 0 (< 11 mitoses/10 hpf; n = 9) was significantly longer than that for dogs with higher scores (indicating higher mitotic rates); the 1-year survival rate for these dogs was 42%.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that future studies should take histologic factors, particularly mitotic rate, as well as tumor stage into account when assessing treatment effects on survival time of dogs with splenic hemangiosarcoma.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine whether a carboplatin dose calculation that is based on a targeted area under the concentration-versus-time curve (AUCTarget) and individual glomerular filtration rate (GFR) accurately predicts carboplatin-associated myelotoxicoses in tumor-bearing cats, and to determine the maximum tolerated AUCTarget.

Animals—32 cats with tumors.

Procedures—In each cat, plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid was measured to assess GFR. Carboplatin was administered IV. The dose was calculated by use of an equation as follows: Dose = AUCTarget × 2.6 × GFR × body weight. Initial AUCTarget was 2.0 min·mg·mL−1 and was increased in increments of 0.50 min·mg·mL−1 in cohorts of 3 cats. To assess myelotoxic effects, CBCs were performed weekly for ≥ 4 weeks. Following identification of the maximum tolerated AUCTarget, additional cats were treated at that AUCTarget and plasma platinum concentrations were measured in 6 cats.

Results—The AUCTarget values ranged from 2.0 to 3.0 min·mg·mL−1. Neutropenia was the dose-limiting toxicosis, and the maximum tolerated AUCTarget was 2.75 min·mg·mL−1. Nineteen cats received this dose of carboplatin; 13 became neutropenic, but only 1 developed severe neutropenia (< 500 neutrophils/μL), and none had neutropenia-associated clinical signs. In the cats that had plasma platinum concentration determined, the difference between AUCTarget and the measured value ranged from −0.23 to 0.31 min·mg·mL−1 (median, 0.20 min·mg·mL−1).

Conclusions and Clinical Relevance—In cats, carboplatin-associated myelotoxicoses were accurately and uniformly predicted by use of the proposed dosing strategy. The maximum tolerated AUCTarget for a single dose of carboplatin was 2.75 min·mg·mL−1.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether a glomerular filtration rate (GFR) assay based on serum iohexol clearance can be used to predict carboplatin clearance in cats.

Animals—10 cats with tumors.

Procedures—GFR was measured concurrently by use of plasma clearance of technetium Tc 99m–labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) to yield GFR99mTc-DTPA and serum clearance of iohexol to yield GFRIohexol. A single dose of carboplatin was administered IV as a bolus. Dose was calculated by use of a target value for the area under the plasma platinum concentration-versus-time curve (AUCTarget) and estimation of platinum clearance (CLPT) derived from GFR99mTc-DTPA as follows: dose = AUCTarget × 2.6 × GFR99mTc-DTPA × body weight, where AUCTarget is 2.75 min·mg·mL−1. Plasma platinum concentrations were measured via atomic absorption spectrophotometry. Values for GFR99mTc-DTPA and GFRIohexol were compared by use of least-squares regression and Bland-Altman analysis. Least-squares regression was used to determine whether CLPT could be predicted from GFR99mTc-DTPA or GFRIohexol (or both).

Results—GFR99mTc-DTPA and GFRIohexol were strongly correlated (r = 0.90), but GFRIohexol values were significantly larger by a factor of approximately 1.4. Platinum clearance had a significant linear relationship to GFR99mTc-DTPA (CLPT = 2.5 × GFR99mTc-DTPA) and to GFRIohexol (CLPT = [1.3 × GFRIohexol] + 1.4).

Conclusions and Clinical Relevance—In cats, serum iohexol clearance was an accurate predictor of CLPT and can be used to calculate the carboplatin dose as follows: dose = AUCTarget × ([1.3 × GFRIohexol] + 1.4) × body weight.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate long-term function of vascular access ports (VAPs) implanted in the femoral vein of dogs and cats undergoing cancer treatment.

Design—Prospective clinical study.

Animals—3 dogs and 6 cats treated via chemotherapy or radiation.

Procedures—VAPs were surgically implanted in the left femoral vein of 3 dogs and 6 cats over a 1-year period. Injection port location was alternated to either a caudal thoracic or ilial location in each patient. Duration of VAP function, ease of infusion, and ease of aspiration through the VAPs were recorded, and associated complications were assessed at each VAP use. Client satisfaction with VAP placement was evaluated by use of a questionnaire.

Results—Primary uses of the VAPs included blood sampling and delivering sedative or chemotherapeutic drugs. Median duration of successful infusion was 147 days (range, 60 to 370 days), and median duration of successful aspiration was 117 days (range, 10 to 271 days). The frequency of signs of VAP-related discomfort was low (7% of patient observations). Clients were satisfied with their decision to use VAPs. Complications included partial (n = 7) or complete (2) VAP occlusion, port migration (1), and presumptive infection (1).

Conclusions and Clinical Relevance—Results suggested that VAP implantation into the femoral vein provides an acceptable means of chronic venous access in dogs and cats undergoing cancer treatment.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Case Description—3 dogs (9 to 12 years old) were evaluated because of recurrent pleural effusion that was refractory to treatment of the underlying cause.

Clinical Findings—Dogs were evaluated because of cough, dyspnea, tachypnea, or lethargy or a combination of these clinical signs. Radiography, ultrasonography, or thoracocentesis were used to confirm the presence of pleural fluid in each dog. A neoplastic cause of pleural effusion was confirmed in 2 dogs. In 1 dog, fasciitis of the mediastinum and the left parietal pleura was diagnosed, with no evidence of neoplasia.

Treatment and Outcome—Each dog was anesthestized, and thoracotomy was performed with manual perforation of the mediastinum. Permanent, subcutaneously placed vascular access ports were attached to intrathoracic, Jackson-Pratt drain tubing for repeated drainage of pleural fluid. Drains were used successfully in the 3 dogs for periods of 6 weeks, 11 weeks, and > 3 years.

Clinical Relevance—Findings suggest that subcutaneous vascular access ports attached to intrathoracic drain tubing may be an effective way to remove recurrent pleural effusion in dogs.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To compare clinical outcome of dogs with cutaneous mast cell tumors (MCTs) in the inguinal or perineal region with outcome for dogs with MCTs in other cutaneous locations.

Design—Retrospective study.

Animals—37 dogs with MCTs in the inguinal or perineal region and 87 dogs with MCTs in other cutaneous locations.

Procedure—Information obtained from the medical records included sex, breed, age, histologic grade of all tumors, number and location of all tumors, tumor size (ie, diameter of the tumor), completeness of surgical excision, treatments administered in addition to surgery, and outcome. In all dogs, the primary treatment consisted of surgical excision.

Results—Disease-free interval and survival time for dogs with MCTs in the inguinal or perineal region were not significantly different from values for dogs with MCTs in other cutaneous locations. Dogs with incompletely excised tumors, dogs with grade III tumors, and dogs that received systemic treatment were 2, 2.5, and 4 times as likely, respectively, to have a relapse. Factors significantly associated with a shorter survival time were age > 8 years, metastatic disease at the time of initial diagnosis, and tumor relapse.

Conclusions and Clinical Relevance—Results of the present study suggest that dogs with MCTs in the inguinal or perineal region do not have a worse prognosis in regard to disease-free interval or survival time than do dogs with MCTs in other cutaneous locations. Treatment recommendations for dogs with cutaneous MCTs should be based on confirmed predictors of biological behavior, such as histologic grade and clinical stage. (J Am Vet Med Assoc 2005;226:1368–1374)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate response rate and duration of malignant melanomas in dogs treated with carboplatin.

Design—Retrospective study.

Animals—27 client-owned dogs with spontaneously occurring measurable malignant melanomas.

Procedure—Records of dogs with melanomas treated with carboplatin from October 1989 to June 2000 were reviewed. Carboplatin was administered IV at doses of 300 or 350 mg/m2 of body surface area. Response to treatment and evidence of drug toxicity were determined.

Result—Response to treatment could be evaluated in 25 dogs. Of those, overall response rate was 28%. One dog had a complete response, 6 (24%) dogs had a partial response (> 50% reduction in tumor burden). Median duration of partial response was 165 days. Eighteen dogs had stable disease (n = 9; 36%) or progressive disease (9; 36%). Response to treatment was significantly associated with carboplatin dose on a milligram per kilogram basis (15.1 mg/kg [6.9 mg/lb] of body weight vs 12.6 mg/kg [5.7 mg/lb]). Evidence of gastrointestinal toxicosis could be assessed in 27 dogs. Mean body weight of 5 dogs that developed gastrointestinal toxicosis was significantly less than that of 22 dogs without gastrointestinal toxicosis (9.9 kg [21.8 lb] vs 19.3 kg [42.5 lb]).

Conclusions and Clinical Relevance—Carboplatin had activity against macroscopic spontaneously occurring malignant melanomas in dogs and should be considered as an adjunctive treatment for microscopic local or metastatic tumors. Gastrointestinal toxicosis was associated with body weight. Because small dogs are more likely to have adverse gastrointestinal effects, gastrointestinal protectants should be considered for these patients. (J Am Vet Med Assoc 2001;218:1444–1448)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of ifosfamide in tumor-bearing cats.

Animals—38 cats with resected, recurrent, or metastatic sarcomas.

Procedure—The starting dosage of ifosfamide was 400 mg/m2 of body surface area, IV, and dosages were increased by 50 to 100 mg/m2 in cohorts of 3 cats. To protect against urotoxicosis, mesna was administered at a dosage equal to 20% of the calculated ifosfamide dosage. Diuresis with saline (0.9% NaCl) solution before and after administration of ifosfamide was used to minimize nephrotoxicosis. Samples for pharmacokinetic analysis were obtained after the MTD was reached.

Results—38 cats were entered into this phase I study and were administered a single dose of ifosfamide at various dosages. The MTD was 1,000 mg/m2, and neutropenia was the DLT. Seven of 8 episodes of neutropenia were on day 7 after treatment, and 1 cat developed severe neutropenia on day 5. Adverse effects on the gastrointestinal tract were generally mild and self-limiting, the most common of which was nausea during ifosfamide infusion. One cat had signs consistent with a drug-induced hypersensitivity reaction. There were no episodes of hemorrhagic cystitis or nephrotoxicosis. Correlations between pharmacokinetic variables and ifosfamide-associated toxicoses were not found. Preliminary evidence of antitumor activity was observed in 6 of 27 cats with measurable tumors.

Conclusions and Clinical Relevance—The dosage of ifosfamide recommended to treat tumor-bearing cats is 900 mg/m2 every 3 weeks. This dosage should be used in phase II clinical trials.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To characterize the pharmacokinetic disposition of carboplatin and determine whether glomerular filtration rate (GFR) could be used to predict carboplatin clearance and myelotoxic effects in cats with tumors.

Animals—10 cats with tumors.

Procedure—Glomerular filtration rate was assessed in each cat by monitoring plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Each cat received carboplatin (200 mg/m2 of body surface area) administered as an IV bolus. Plasma platinum concentrations were measured via atomic absorption spectrophotometry, and pharmacokinetic analysis was performed. A CBC was performed weekly for each cat, and the correlation between the area under the concentration-versus-time curve (AUC) and the severity of myelosuppression was calculated. Least squares regression analysis was performed to determine whether GFR could be used to predict plasma platinum clearance (ClPt).

Results—For all cats, AUC measurements ranged from 0.99 to 4.30 min·mg·mL–1. Neutrophil concentration nadirs were detected 1 to 3 weeks after treatment and ranged from 200 to 8,000 cells/µL. The absolute neutrophil concentration at the nadir was inversely correlated with AUC. The ClPt was predicted by use of GFR measurements (ClPt = 2.60 × GFR). A carboplatin dose prescription model was derived involving AUC, estimated ClPt, and body weight in kilograms (BWkg), in which dose = AUC × 2.60(GFR) × BWkg.

Conclusions and Clinical Relevance—In cats, an individualized prescription strategy for carboplatin administration based on a targeted AUC and determination of GFR might more uniformly predict myelosuppression than that predicted by conventional dosing based on body surface area. (Am J Vet Res 2004;65:1502–1507)

Full access
in American Journal of Veterinary Research