Thesis
INVESTIGATING THE PLASMA PHARMACOKINETICS OF ORAL CAPECITABINE CHEMOTHERAPY IN CARCINOMA-BEARING DOGS
Washington State University
Master of Science (MS), Washington State University
01/2021
DOI:
https://doi.org/10.7273/000002442
Handle:
https://hdl.handle.net/2376/122118
Abstract
Canine malignant cancers are a devastating reality to many pet owners. Oral chemotherapy has become increasingly popular as a treatment option due to many factors, including decreased cost, fewer veterinary visits, and ease of administration, however, there are still few oral chemotherapy options available in veterinary medicine. Capecitabine is an oral prodrug of the active metabolite 5-fluorouracil, which has been used effectively in human colorectal, head and neck, and mammary carcinomas. Capecitabine has several properties that make it an attractive treatment option for dogs: (i) it is relatively inexpensive, (ii) it has a short half-life in humans, allowing for quick dose adjustments if side effects are noted, and (iii) it is effective for treating carcinomas, for which there are no widely–effective oral chemotherapy options in dogs. As part of our efforts to determine if capecitabine is a viable treatment option for canine carcinomas, we aimed to determine the pharmacokinetics of capecitabine in 5 dogs with naturally occurring carcinomas. We also aimed to report adverse events and treatment responses associated with administration of oral capecitabine over a 5-week period.
Capecitabine was well tolerated when dosed at 750 mg/m2 by mouth once daily for two weeks followed by a week off and then an additional 2 weeks of daily capecitabine. No dogs withdrew from the study due to adverse events or other causes. The median AUC0-24 h was 1012.4 h*ng/ml (range 773.0-1141.4 h*ng/ml), however, the maximum blood concentration and time to reach that concentration of capecitabine was highly variable after a single dose. Two dogs (40%) had a biologic response at 5 weeks after beginning treatment and maintained stable disease to the end of data collection.
This study suggests that capecitabine holds promise as an oral chemotherapy agent for dogs with carcinomas, although individualized dosing may be necessary, and further studies are warranted.
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Details
- Title
- INVESTIGATING THE PLASMA PHARMACOKINETICS OF ORAL CAPECITABINE CHEMOTHERAPY IN CARCINOMA-BEARING DOGS
- Creators
- Sarah Marie Wetzel
- Contributors
- Janean Fidel (Advisor)Nicolas Villarino (Committee Member)Rance Sellon (Committee Member)K. Jane Wardrop (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Number of pages
- 32
- Identifiers
- 99900606854701842
- Language
- English
- Resource Type
- Thesis