A Pilot Phase II Study of the Efficacy and Biosafety of Doxorubicin Chemotherapy in Tumor‐Bearing Equidae. (20th September 2013)

• Record Type: Journal Article
• Authors: Théon, A.P.; Pusterla, N.; Magdesian, K.G.; Wittenburg, L.; Marmulak, T.; Wilson, W.D.
• Is Part Of: Journal of veterinary internal medicine. Volume 27:Number 6(2013:Nov./Dec.)
• Page Start: 1581
• Page End: 1588
• Publication Date: 2013-09-20
• Subjects: Veterinary medicine -- Periodicals; 636.0896
• DOI: 10.1111/jvim.12144
• Languages: English
• ISSNs: 0891-6640

Abstract

<abstract abstract-type="main" id="jvim12144-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jvim12144-sec-0001" sec-type="section"> <title>Background</title> <p>The efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses.</p> </sec> <sec id="jvim12144-sec-0002" sec-type="section"> <title>Objectives</title> <p>To provide preliminary evidence of the efficacy of doxorubicin in tumor‐bearing horses, explore drug pharmacokinetics profile, and estimate period of risk of exposure to drug residues.</p> </sec> <sec id="jvim12144-sec-0003" sec-type="section"> <title>Animals</title> <p>Twelve horses with 37 tumors.</p> </sec> <sec id="jvim12144-sec-0004" sec-type="section"> <title>Procedures</title> <p>Treatment protocol included 6 treatments at 3‐week intervals. Eight horses were uniformly treated at a dosage of 70 mg/m<sup>2</sup> and 4 horses received 4 of 6 treatment cycles at 70 mg/m<sup>2</sup>. Clinical signs, tumor responses, and toxicoses were evaluated. Drug residue concentrations were quantitated in 3 horses receiving of 65, 70, and 75 mg/m<sup>2</sup> by high‐performance liquid chromatography with ultraviolet detection (plasma, feces) and liquid chromatography and tandem mass spectrometry (urine).</p> </sec> <sec id="jvim12144-sec-0005" sec-type="section"> <title>Results</title> <p>Thirty tumors, including lymphomas, carcinomas, sarcoids, and melanoma, were evaluated for efficacy. The overall response rate was 47% (95% CI, 28–65%). Doxorubicin was not found to be effective against melanomas. Lymphomas and carcinomas were most responsive. Pooled serum Cmax and half‐life of doxorubicin were 121.3 ng/mL and 12.9 hours, respectively. There were no detectable residues in fecal samples up to 3 weeks after treatment and in plasma and urine after 2 and 3 days, respectively.</p> </sec> <sec id="jvim12144-sec-0006" sec-type="section"> <title>Conclusion and Clinical Relevance</title> <p>This study provides preliminary evidence that single‐agent doxorubicin at a dosage of 70 mg/m<sup>2</sup> has a broad spectrum of activity. The risk of exposure to drug residues in plasma and feces was low. Direct contact with urine‐contaminated wastes should be avoided for 2 days after treatment.</p> </sec> </abstract>