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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 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 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

Abstract

OBJECTIVE To evaluate platinum content in biodegradable carboplatin-impregnated beads and retrospectively assess tolerability and outcome data for dogs treated by intralesional placement of such beads following surgical excision of subcutaneous sarcomas.

DESIGN Evaluation study and retrospective case series.

SAMPLE 9 carboplatin-impregnated beads and 29 client-owned dogs.

PROCEDURES Platinum content in 9 carboplatin-impregnated beads from 3 lots was measured by spectrophotometry, and calculated carboplatin content was compared with the labeled content. Medical records were searched to identify dogs with subcutaneous sarcomas for which treatment included placement of carboplatin-impregnated beads between 2011 and 2014. Signalment, tumor characteristics, surgical and histologic data, adverse events, and local recurrences were recorded. Associations between variables of interest and adverse events or local disease-free interval were analyzed.

RESULTS In vitro analysis identified a mean ± SD platinum content of 5.38 ± 0.97 mg/bead. Calculated carboplatin content (10.24 ± 1.84 mg/bead) was significantly greater than the labeled amount (4.6 mg/bead). Bead weight and total platinum content differed significantly among lots, but platinum content per bead weight did not. Mild-to-moderate local adverse events were reported for 11 of 29 tumors; all resolved without additional surgery. No dogs had signs of systemic toxicosis. Overall local disease-free rates 1, 2, and 3 years after surgery were 70%, 70%, and 58%, respectively, as determined by Kaplan-Meier analysis.

CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated beads were well tolerated; however, results of in vitro tests indicated that caution is needed because of manufacturing inconsistencies.

Restricted access
in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE

To evaluate survival times for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone.

ANIMALS

109 client-owned dogs recruited from 15 institutions in the United States.

PROCEDURES

Dogs were treated with prednisone at a dosage of 40 mg/m2, PO, once daily for 7 days and at a dosage of 20 mg/m2, PO, once daily thereafter. Quality of life (QOL) was assessed by owners with a visual analog scale when treatment was started (day 0), 1 and 2 weeks after treatment was started, and every 4 weeks thereafter. The primary outcome of interest was survival time as determined by the Kaplan-Meier method. Factors potentially associated with survival time were examined.

RESULTS

Median overall survival time was 50 days (95% CI, 41 to 59 days). Factors associated with survival time included substage (a vs b) and immunopheno-type (B cell vs T cell). Owner-assigned QOL scores on days 0 and 14 were significantly positively correlated with survival time. When QOL score was dichotomized, dogs with day 0 or day 14 QOL scores ≥ 50 had significantly longer survival times, compared with dogs with day 0 or day 14 QOL scores < 50. No variables were predictive of long-term (> 120 days) survival.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that survival times were short for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone. Owner-perceived QOL and clinician-assigned sub-stage were both associated with survival time. Findings provide potentially important information for clinicians to discuss with owners of dogs with lymphoma at the time treatment decisions are made. (J Am Vet Med Assoc 2021;259:62–71)

Restricted access
in Journal of the American Veterinary Medical Association