An Open-label Phase 1 Dose-escalation Clinical Trial of a Single Intravenous Administration of Gemcitabine in Dogs with Advanced Solid Tumors


Marconato, L, Finotello, R ORCID: 0000-0002-1932-211X, Bonfanti, U, Dacasto, M, Beatrice, L, Pizzoni, S, Leone, VF, Balestra, G, Furlanello, T, Bley, C Rohrer et al (show 1 more authors) (2015) An Open-label Phase 1 Dose-escalation Clinical Trial of a Single Intravenous Administration of Gemcitabine in Dogs with Advanced Solid Tumors. JOURNAL OF VETERINARY INTERNAL MEDICINE, 29 (2). pp. 620-625.

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Abstract

<h4>Background</h4>A broad range of gemcitabine dosages have been used in dogs.<h4>Hypothesis/objectives</h4>To determine maximally tolerated dose (MTD), dose-limiting toxicity (DLT), and preliminary antitumor activity of intravenous administration of gemcitabine in dogs with advanced solid tumors.<h4>Animals</h4>Twenty-two client-owned dogs.<h4>Methods</h4>Dogs with advanced cancer were prospectively enrolled in an open-label Phase 1 study of gemcitabine. Gemcitabine was administered as a 30-minute intravenous bolus starting at 800 mg/m(2), using escalation of 50 mg/m(2) increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Treatment continued until disease progression or unacceptable toxicosis. Additional dogs were enrolled at MTD to better characterize tolerability, and to assess the extent and duration of gemcitabine excretion.<h4>Results</h4>Twenty-two dogs were treated at 4 dose levels, ranging from 800 to 950 mg/m(2). Neutropenia was identified as DLT. MTD was 900 mg/m(2). DLT consisting of grade 4 febrile neutropenia was observed at 950 mg/m(2) in 2 dogs. There were no nonhematologic DLTs. Twenty dogs received multiple doses, and none had evidence of severe toxicosis from any of their subsequent treatments. At 900 mg/m(2), 2 complete and 5 partial responses were observed in dogs with measurable tumors. The amount of gemcitabine excreted in urine decreased over time, and was undetectable after the first 24 hours.<h4>Conclusions and clinical importance</h4>The recommended dose of gemcitabine for future Phase 2 studies is weekly 900 mg/m(2). In chemotherapy-naïve dogs with advanced solid tumor this dose level merits further evaluation.

Item Type: Article
Uncontrolled Keywords: Canine, Dose-limiting toxicity, Gemzar, Maximally tolerated dose
Depositing User: Symplectic Admin
Date Deposited: 21 Sep 2015 09:05
Last Modified: 20 Jan 2023 01:52
DOI: 10.1111/jvim.12557
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/2026859
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