Plasma Cytokeratin 18 and fecal Alpha-1 Antitrypsin concentrations in dogs with osteosarcoma receiving carboplatin chemotherapy.
chemotherapy-associated gastrointestinal toxicity
cytotoxic chemotherapy
gastrointestinal tract
neoplasia
Journal
Veterinary medicine and science
ISSN: 2053-1095
Titre abrégé: Vet Med Sci
Pays: England
ID NLM: 101678837
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
revised:
15
09
2020
received:
07
05
2020
accepted:
25
10
2020
pubmed:
23
11
2020
medline:
21
10
2021
entrez:
22
11
2020
Statut:
ppublish
Résumé
Gastrointestinal (GI) toxicosis is a common side effect of cytotoxic chemotherapy treatment in humans and dogs. Measurement of cytokeratin 18 (CK18), an intracellular structural protein released during epithelial apoptosis, and Alpha1-Antitrypsin (A1AT) in faeces provides a mechanism for evaluating damage to the intestinal mucosa secondary to cytotoxic chemotherapy. Our goal was to evaluate the clinical utility of plasma CK18 and faecal A1-AT levels as non-invasive biomarkers of cytotoxic chemotherapy induced GI toxicity. We conducted a prospective cohort study in dogs (N = 10) with osteosarcoma undergoing amputation followed by carboplatin chemotherapy. We hypothesized that plasma CK18 and faecal A1-AT levels would increase following carboplatin administration due to drug-induced GI epithelial damage/apoptosis, and that plasma CK18 and faecal A1-AT levels would correlate with severity of GI toxicity. Mean baseline plasma CK18 concentration was variable amongst patients; however, CK18 concentration prior to carboplatin chemotherapy treatment was not significantly different from CK18 levels after treatment. There was significant intra and inter-patient variability in mean faecal A1-AT levels at baseline. Mean A1-AT concentration did not change significantly from day 0 to day 21. Gastrointestinal toxicity was minimal; therefore, we were unable to determine the association of plasma CK18 and faecal A1-AT concentrations with development of GI toxicosis. In this study population, plasma CK18 and faecal A1-AT concentration were not clinically useful biomarkers for the detection of GI toxicosis secondary to carboplatin administration. Further prospective evaluation of CK18 and A1-AT as biomarkers of drug-induced GI toxicity is warranted in a larger cohort of dogs receiving cytotoxic chemotherapy. AVMA clinical trial registration number: AAHSD004827.
Identifiants
pubmed: 33222415
doi: 10.1002/vms3.392
pmc: PMC8025642
doi:
Substances chimiques
Antineoplastic Agents
0
Keratin-18
0
alpha 1-Antitrypsin
0
Carboplatin
BG3F62OND5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
385-392Subventions
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NIH HHS
ID : K01 OD019923
Pays : United States
Informations de copyright
© 2020 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.
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