PMID- 32510792
OWN - NLM
STAT- MEDLINE
DCOM- 20210908
LR  - 20210908
IS  - 1476-5829 (Electronic)
IS  - 1476-5810 (Linking)
VI  - 18
IP  - 4
DP  - 2020 Dec
TI  - An open-label dose escalation study evaluating tolerability and safety of a 
      single 5-days course of temozolomide in dogs with advanced cancer.
PG  - 838-842
LID - 10.1111/vco.12623 [doi]
AB  - 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/m(2) , using escalation of 10 
      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. Safety evaluation was 
      performed 10 days after dosing. Thirty-three client-owned dogs were enrolled. MTD 
      was established at 150 mg/m(2) 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/m(2) . A subcohort of dogs 
      received multiple temozolomide doses on a 4-week cycle and no cumulative toxicity 
      was documented. Conclusions of this study define temozolomide MTD at 150 mg/m(2) 
      when given once daily over 5 days. Future trials on the efficacy of temozolomide 
      administered at its MTD are warranted.
CI  - (c) 2020 John Wiley & Sons Ltd.
FAU - Marconato, Laura
AU  - Marconato L
AUID- ORCID: 0000-0002-7843-615X
AD  - Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
FAU - Rohrer Bley, Carla
AU  - Rohrer Bley C
AUID- ORCID: 0000-0002-5733-2722
AD  - Division of Radiation Oncology, Vetsuisse Faculty, University of Zurich, Zurich, 
      Switzerland.
FAU - Leone, Vito F
AU  - Leone VF
AD  - Centro Oncologico Veterinario, Bologna, Italy.
FAU - Finotello, Riccardo
AU  - Finotello R
AD  - Department of Small Animal Clinical Science, Institute of Veterinary Science, 
      University of Liverpool, Neston, UK.
LA  - eng
PT  - Clinical Trial, Veterinary
PT  - Journal Article
DEP - 20200705
PL  - England
TA  - Vet Comp Oncol
JT  - Veterinary and comparative oncology
JID - 101185242
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/*pharmacology
MH  - Dog Diseases/blood/*drug therapy
MH  - Dogs
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Male
MH  - Neoplasms/drug therapy/veterinary/*virology
MH  - Temozolomide/*pharmacology
OTO - NOTNLM
OT  - DLT
OT  - MTD
OT  - canine
OT  - phase 1
OT  - temozolomide
EDAT- 2020/06/09 06:00
MHDA- 2021/09/09 06:00
CRDT- 2020/06/09 06:00
PHST- 2020/03/20 00:00 [received]
PHST- 2020/05/28 00:00 [revised]
PHST- 2020/05/31 00:00 [accepted]
PHST- 2020/06/09 06:00 [pubmed]
PHST- 2021/09/09 06:00 [medline]
PHST- 2020/06/09 06:00 [entrez]
AID - 10.1111/vco.12623 [doi]
PST - ppublish
SO  - Vet Comp Oncol. 2020 Dec;18(4):838-842. doi: 10.1111/vco.12623. Epub 2020 Jul 5.