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Use of Epothilone B (Patupilone) in Refractory Lymphoma and advanced solid tumors in dogs


Meier, Valeria Sabina; Geigy, Caroline; Grosse, Nicole; McSheehy, Paul M J; Rohrer Bley, Carla (2013). Use of Epothilone B (Patupilone) in Refractory Lymphoma and advanced solid tumors in dogs. Journal of Veterinary Internal Medicine, 27(1):120-125.

Abstract

Background: The epothilones are microtubule-stabilizing agents with promising antitumor effect in refractory and metastatic tumors in humans. The toxicity profile is considered more favorable than in taxanes. The safety of epothilone B (patupilone) has not been evaluated in tumor-bearing dogs.
Objectives: To evaluate the inhibition of proliferation in canine tumor cells after patupilone treatment. To assess toxicity profile and maximally tolerated dose of patupilone in dogs with refractory tumors.
Animals: Twenty client-owned dogs with various malignancies.
Methods: The inhibition of proliferation was assessed with a proliferation assay in vitro in canine hemangiosarcoma and lymphoma cell lines. In the prospective clinical study, dogs received patupilone intravenously once a week for two treatments (= one treatment cycle). Dose was escalated with three dogs per cohort and 20% increments. Adverse effects were graded according to the VCOG-CTCAE v1.0.
Results: Both canine cell lines were sensitive to patupilone with approximately 50% decrease of proliferative activity at 0.2-1 nM. In vivo, dose-limiting adverse effects occurred at 3.3 mg/m2; main adverse effects were diarrhea, anorexia, vomiting, and nausea. Neither neutropenia nor peripheral neuropathy was observed. Maximally tolerated dose for two patupilone administrations once weekly IV is 2.76 mg/m2. 3/11 dogs receiving more than one treatment cycle showed partial remission in the short period of observation.
Conclusions and Clinical Importance: Canine tumor cells show inhibition of proliferation to patupilone in vitro. Clinically, a dose of 2.76 mg/m2 IV is well tolerated in dogs with spontaneously occurring tumors.

Abstract

Background: The epothilones are microtubule-stabilizing agents with promising antitumor effect in refractory and metastatic tumors in humans. The toxicity profile is considered more favorable than in taxanes. The safety of epothilone B (patupilone) has not been evaluated in tumor-bearing dogs.
Objectives: To evaluate the inhibition of proliferation in canine tumor cells after patupilone treatment. To assess toxicity profile and maximally tolerated dose of patupilone in dogs with refractory tumors.
Animals: Twenty client-owned dogs with various malignancies.
Methods: The inhibition of proliferation was assessed with a proliferation assay in vitro in canine hemangiosarcoma and lymphoma cell lines. In the prospective clinical study, dogs received patupilone intravenously once a week for two treatments (= one treatment cycle). Dose was escalated with three dogs per cohort and 20% increments. Adverse effects were graded according to the VCOG-CTCAE v1.0.
Results: Both canine cell lines were sensitive to patupilone with approximately 50% decrease of proliferative activity at 0.2-1 nM. In vivo, dose-limiting adverse effects occurred at 3.3 mg/m2; main adverse effects were diarrhea, anorexia, vomiting, and nausea. Neither neutropenia nor peripheral neuropathy was observed. Maximally tolerated dose for two patupilone administrations once weekly IV is 2.76 mg/m2. 3/11 dogs receiving more than one treatment cycle showed partial remission in the short period of observation.
Conclusions and Clinical Importance: Canine tumor cells show inhibition of proliferation to patupilone in vitro. Clinically, a dose of 2.76 mg/m2 IV is well tolerated in dogs with spontaneously occurring tumors.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinary Clinic > Department of Small Animals
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:Microtubule-stabilizing agents, epothilones, chemotherapy
Language:English
Date:2013
Deposited On:27 Dec 2012 14:51
Last Modified:07 Dec 2017 17:23
Publisher:Wiley-Blackwell
ISSN:0891-6640
Publisher DOI:https://doi.org/10.1111/jvim.12019
PubMed ID:23205945

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