An open-label dose escalation study evaluating tolerability and safety of a single 5-days course of temozolomide in dogs with advanced cancer.

Veterinary and Comparative Oncology
L MarconatoR Finotello

Abstract

Temozolomide is a novel oral alkylating agent that has schedule-dependent clinical activity in human malignant glioma and metastatic melanoma. Little is known about the efficacy of temozolomide in the treatment of canine solid cancers, where broad range of dosages have been used but no maximally tolerated dose (MTD) had been established. The aim of this this open-label, dose-escalating study was to determine MTD and dose-limiting toxicity (DLT) of a single temozolomide cycle in dogs with advanced solid tumours. Temozolomide was administered as a 5-days course starting at 70 mg/m2 , using escalation of 10 mg/m2 increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Safety evaluation was performed 10 days after dosing. Thirty-three client-owned dogs were enrolled. MTD was established at 150 mg/m2 and the most frequent adverse events (AEs) were hematologic and hepatic, followed by gastrointestinal, with the majority being self-resolving and of mild grade. VCOG grade 3 hepatic toxicity and grade 4 thrombocytopenia were defined as DLTs at 160 mg/m2 . A subcohort of dogs received multiple temozolomide doses on a 4-week cycle and no cumulative toxicity was docume...Continue Reading

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Citations

Sep 4, 2021·Veterinary Medicine and Science·Nina Simona TreschKatarzyna J Nytko

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