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Metronomic administration of chlorambucil for treatment of dogs with urinary bladder transitional cell carcinoma

Diane R. SchremppDepartment of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907.

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Michael O. ChildressDepartment of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907.

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Jane C. StewartDepartment of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907.

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Tiffany N. LeachDepartment of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907.

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Kean Ming TanDepartment of Statistics, Purdue University, West Lafayette, IN 47907.

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Andrew H. AbboDepartment of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907.

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Amalia E. de GortariDepartment of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907.

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Patty L. BonneyDepartment of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907.

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Deborah W. KnappDepartment of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907.
Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907.

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Abstract

Objective—To determine the antitumor effects and toxicoses of metronomic oral administration of a low dose of chlorambucil in dogs with transitional cell carcinoma (TCC).

Design—Prospective clinical trial.

Animals—31 client-owned dogs with TCC for which prior treatments had failed or owners had declined other treatments.

Procedures—Chlorambucil (4 mg/m2, PO, q 24 h) was administered to dogs. Before and at scheduled times during treatment, evaluations of dogs included physical examination, CBC, serum biochemical analyses, urinalysis, thoracic and abdominal imaging including cystosonography for measurement of TCCs, and grading of toxicoses.

Results—29 of 31 dogs had failed prior TCC treatment. Of the 30 dogs with available data, 1 (3%) had partial remission (≥ 50% reduction in tumor volume), 20 (67%) had stable disease (< 50% change in tumor volume), and 9 (30%) had progressive disease (≥ 50% increase in tumor volume or development of additional tumors); 1 dog was lost to follow-up. The median progression-free interval (time from the start of chlorambucil treatment to the day progressive disease was detected) for the dogs was 119 days (range, 7 to 728 days). The median survival time of dogs from the time of the start of chlorambucil treatment was 221 days (range, 7 to 747 days). Few toxicoses were detected; chlorambucil administration was discontinued because of toxicoses in only 1 dog.

Conclusions and Clinical Relevance—Metronomic administration of chlorambucil was well tolerated, and 70% of dogs had partial remission or stable disease. Metronomic administration of chlorambucil may be a treatment option for dogs with TCC.

Abstract

Objective—To determine the antitumor effects and toxicoses of metronomic oral administration of a low dose of chlorambucil in dogs with transitional cell carcinoma (TCC).

Design—Prospective clinical trial.

Animals—31 client-owned dogs with TCC for which prior treatments had failed or owners had declined other treatments.

Procedures—Chlorambucil (4 mg/m2, PO, q 24 h) was administered to dogs. Before and at scheduled times during treatment, evaluations of dogs included physical examination, CBC, serum biochemical analyses, urinalysis, thoracic and abdominal imaging including cystosonography for measurement of TCCs, and grading of toxicoses.

Results—29 of 31 dogs had failed prior TCC treatment. Of the 30 dogs with available data, 1 (3%) had partial remission (≥ 50% reduction in tumor volume), 20 (67%) had stable disease (< 50% change in tumor volume), and 9 (30%) had progressive disease (≥ 50% increase in tumor volume or development of additional tumors); 1 dog was lost to follow-up. The median progression-free interval (time from the start of chlorambucil treatment to the day progressive disease was detected) for the dogs was 119 days (range, 7 to 728 days). The median survival time of dogs from the time of the start of chlorambucil treatment was 221 days (range, 7 to 747 days). Few toxicoses were detected; chlorambucil administration was discontinued because of toxicoses in only 1 dog.

Conclusions and Clinical Relevance—Metronomic administration of chlorambucil was well tolerated, and 70% of dogs had partial remission or stable disease. Metronomic administration of chlorambucil may be a treatment option for dogs with TCC.

Contributor Notes

Dr. Schrempp's present address is VCA Veterinary Care Animal Hospital and Referral Center, 9901 Montgomery Blvd, Albuquerque, NM 87111.

Mr. Tan's present address is Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA 98195.

Dr. Leach's present address is Veterinary Specialty Center, 1515 Busch Pkwy, Buffalo Grove, IL 60089.

Dr. Abbo's present address is New England Veterinary Oncology Group, 180 Bear Hill Road, Waltham, MA 02451.

Supported in part by private donations made for bladder cancer research at Purdue University.

Presented as a podium presentation at the 30th Annual Veterinary Cancer Society Conference, San Diego, October 2010.

Address correspondence to Dr. Knapp (knappd@purdue.edu).