Phase I dose escalation study of 12b80 (hydroxybisphosphonate linked doxorubicin) in naturally occurring osteosarcoma.
bisphosphonate
bone targeting
canine
doxorubicin
osteosarcoma
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
17 Nov 2020
17 Nov 2020
Historique:
received:
21
09
2020
accepted:
27
10
2020
entrez:
27
11
2020
pubmed:
28
11
2020
medline:
28
11
2020
Statut:
epublish
Résumé
12b80 combines doxorubicin bound to a bone targeting hydroxybisphosphonate vector using a pH-sensitive linker, designed to specifically trigger doxorubicin release in an acidic bone tumor microenvironment. This phase I study aimed to determine the safety and toxicity profiles of 12b80 in dogs with naturally occurring osteosarcoma, with the objective to translate findings from dogs to humans. Ten client-owned dogs with osteosarcoma were enrolled in an accelerated dose-titration design followed by 3 + 3 design. Dogs received three cycles of 12b80 intravenous injection at 4 mg/kg ( The MTD of 12b80 was 8 mg/kg (i.e., equivalent dose of doxorubicin of 110 mg/m In dogs, 12b80 is overall well tolerated and expends the MTD of doxorubicin up to four times the standard dose of 30 mg/m
Identifiants
pubmed: 33245733
doi: 10.18632/oncotarget.27801
pii: 27801
pmc: PMC7679038
doi:
Types de publication
Journal Article
Langues
eng
Pagination
4281-4292Informations de copyright
Copyright: © 2020 Boyé et al.
Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.
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