A pilot phase II study of the efficacy and biosafety of doxorubicin chemotherapy in tumor-bearing equidae

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Abstract

Background: The efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses. Objectives: 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. Animals: Twelve horses with 37 tumors. Procedures: Treatment protocol included 6 treatments at 3-week intervals. Eight horses were uniformly treated at a dosage of 70 mg/m2 and 4 horses received 4 of 6 treatment cycles at 70 mg/m2. Clinical signs, tumor responses, and toxicoses were evaluat Drug residue concentrations were quantitated in 3 horses receiving of 65, 70, and 75 mg/m2 by high-performance liquid chromatography with ultraviolet detection (plasma, feces) and liquid chromatography and tandem mass spectrometry (urine). Results: 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. Conclusion and Clinical Relevance: This study provides preliminary evidence that single-agent doxorubicin at a dosage of 70 mg/m2 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.

Original languageEnglish (US)
Pages (from-to)1581-1588
Number of pages8
JournalJournal of Veterinary Internal Medicine
Volume27
Issue number6
DOIs
StatePublished - Nov 2013

Fingerprint

Equidae
biosafety
doxorubicin
Doxorubicin
Horses
drug therapy
Drug Residues
horses
Drug Therapy
drug residues
neoplasms
Neoplasms
urine
Urine
melanoma
lymphoma
Feces
carcinoma
Melanoma
Lymphoma

Keywords

  • Chemotherapy
  • Doxorubicin
  • Equine
  • Oncology

ASJC Scopus subject areas

  • veterinary(all)

Cite this

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title = "A pilot phase II study of the efficacy and biosafety of doxorubicin chemotherapy in tumor-bearing equidae",
abstract = "Background: The efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses. Objectives: 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. Animals: Twelve horses with 37 tumors. Procedures: Treatment protocol included 6 treatments at 3-week intervals. Eight horses were uniformly treated at a dosage of 70 mg/m2 and 4 horses received 4 of 6 treatment cycles at 70 mg/m2. Clinical signs, tumor responses, and toxicoses were evaluat Drug residue concentrations were quantitated in 3 horses receiving of 65, 70, and 75 mg/m2 by high-performance liquid chromatography with ultraviolet detection (plasma, feces) and liquid chromatography and tandem mass spectrometry (urine). Results: 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. Conclusion and Clinical Relevance: This study provides preliminary evidence that single-agent doxorubicin at a dosage of 70 mg/m2 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.",
keywords = "Chemotherapy, Doxorubicin, Equine, Oncology",
author = "Theon, {Alain P} and Nicola Pusterla and Magdesian, {K G} and Wittenburg, {Luke Anthony} and T. Marmulak and Wilson, {William D}",
year = "2013",
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T1 - A pilot phase II study of the efficacy and biosafety of doxorubicin chemotherapy in tumor-bearing equidae

AU - Theon, Alain P

AU - Pusterla, Nicola

AU - Magdesian, K G

AU - Wittenburg, Luke Anthony

AU - Marmulak, T.

AU - Wilson, William D

PY - 2013/11

Y1 - 2013/11

N2 - Background: The efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses. Objectives: 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. Animals: Twelve horses with 37 tumors. Procedures: Treatment protocol included 6 treatments at 3-week intervals. Eight horses were uniformly treated at a dosage of 70 mg/m2 and 4 horses received 4 of 6 treatment cycles at 70 mg/m2. Clinical signs, tumor responses, and toxicoses were evaluat Drug residue concentrations were quantitated in 3 horses receiving of 65, 70, and 75 mg/m2 by high-performance liquid chromatography with ultraviolet detection (plasma, feces) and liquid chromatography and tandem mass spectrometry (urine). Results: 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. Conclusion and Clinical Relevance: This study provides preliminary evidence that single-agent doxorubicin at a dosage of 70 mg/m2 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.

AB - Background: The efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses. Objectives: 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. Animals: Twelve horses with 37 tumors. Procedures: Treatment protocol included 6 treatments at 3-week intervals. Eight horses were uniformly treated at a dosage of 70 mg/m2 and 4 horses received 4 of 6 treatment cycles at 70 mg/m2. Clinical signs, tumor responses, and toxicoses were evaluat Drug residue concentrations were quantitated in 3 horses receiving of 65, 70, and 75 mg/m2 by high-performance liquid chromatography with ultraviolet detection (plasma, feces) and liquid chromatography and tandem mass spectrometry (urine). Results: 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. Conclusion and Clinical Relevance: This study provides preliminary evidence that single-agent doxorubicin at a dosage of 70 mg/m2 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.

KW - Chemotherapy

KW - Doxorubicin

KW - Equine

KW - Oncology

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DO - 10.1111/jvim.12144

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