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Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin

BACKGROUND: Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diu...

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Autores principales: Henry, C.J., Flesner, B.K., Bechtel, S.A., Bryan, J.N., Tate, D.J., Selting, K.A., Lattimer, J.C., Bryan, M.E., Grubb, L., Hausheer, F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787204/
https://www.ncbi.nlm.nih.gov/pubmed/29080252
http://dx.doi.org/10.1111/jvim.14848
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author Henry, C.J.
Flesner, B.K.
Bechtel, S.A.
Bryan, J.N.
Tate, D.J.
Selting, K.A.
Lattimer, J.C.
Bryan, M.E.
Grubb, L.
Hausheer, F.
author_facet Henry, C.J.
Flesner, B.K.
Bechtel, S.A.
Bryan, J.N.
Tate, D.J.
Selting, K.A.
Lattimer, J.C.
Bryan, M.E.
Grubb, L.
Hausheer, F.
author_sort Henry, C.J.
collection PubMed
description BACKGROUND: Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans. HYPOTHESIS/OBJECTIVES: We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept. ANIMALS: Fourteen client‐owned dogs were prospectively enrolled. METHODS: Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia. RESULTS: A 90‐minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted.
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spelling pubmed-57872042018-02-08 Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin Henry, C.J. Flesner, B.K. Bechtel, S.A. Bryan, J.N. Tate, D.J. Selting, K.A. Lattimer, J.C. Bryan, M.E. Grubb, L. Hausheer, F. J Vet Intern Med SMALL ANIMAL BACKGROUND: Transitional cell carcinoma is the most common bladder cancer of dogs. Cisplatin combined with piroxicam provides superior response rates, but unacceptable rates of nephrotoxicity. Tavocept is a chemoprotectant that has mitigated cisplatin toxicity and decreased the required infusion/diuresis volume in clinical trials in humans. HYPOTHESIS/OBJECTIVES: We hypothesized that Tavocept would decrease diuresis volume and time and facilitate safe administration of a cisplatin/piroxicam protocol to dogs with bladder cancer. Secondary objectives were to compare response rate and survival times to an historical comparator group treated without Tavocept. ANIMALS: Fourteen client‐owned dogs were prospectively enrolled. METHODS: Tumor volume was measured by computed tomography at days 0, 42, and 84. Dogs received combination Tavocept/cisplatin with a shortened diuresis protocol. A total of 4 doses was planned, with concurrent administration of piroxicam. Serial biochemical analyses were evaluated for azotemia. RESULTS: A 90‐minute infusion/diuresis time was used for all dogs. Three dogs (21%) had concurrent increases in serum creatinine (>2.0 mg/dL) and BUN (>42 mg/dL) concentrations; 2 of these dogs were isosthenuric. This frequency of nephrotoxicity is significantly less (P = 0.0406) than that of an historical control group treated without Tavocept. Overall response rate was 27%. Median survival time was comparable to historical controls (253 vs. 246 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia. Survival time was comparable, but the response rate was inferior to an historical comparator group. Further evaluation in other tumors susceptible to platinum agents is warranted. John Wiley and Sons Inc. 2017-10-27 2018 /pmc/articles/PMC5787204/ /pubmed/29080252 http://dx.doi.org/10.1111/jvim.14848 Text en Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle SMALL ANIMAL
Henry, C.J.
Flesner, B.K.
Bechtel, S.A.
Bryan, J.N.
Tate, D.J.
Selting, K.A.
Lattimer, J.C.
Bryan, M.E.
Grubb, L.
Hausheer, F.
Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin
title Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin
title_full Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin
title_fullStr Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin
title_full_unstemmed Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin
title_short Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin
title_sort clinical evaluation of tavocept to decrease diuresis time and volume in dogs with bladder cancer receiving cisplatin
topic SMALL ANIMAL
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787204/
https://www.ncbi.nlm.nih.gov/pubmed/29080252
http://dx.doi.org/10.1111/jvim.14848
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