Phase I dose escalation study of 12b80 ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
Phase I dose escalation study of 12b80 (hydroxybisphosphonate linked doxorubicin) in naturally occurring osteosarcoma.
Author(s) :
Boyé, P. [Auteur]
Oncovet
David, E. [Auteur]
Atlanthera
Serres, F. [Auteur]
Oncovet
Pascal, Q. [Auteur]
Floch, F. [Auteur]
Geeraert, K. [Auteur]
Coste, V. [Auteur]
Marescaux, L. [Auteur]
Cagnol, S. [Auteur]
Atlanthera
Goujon, J. Y. [Auteur]
Egorov, M. [Auteur]
Le Bot, R. [Auteur]
Tierny, Dominique [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Oncovet
David, E. [Auteur]
Atlanthera
Serres, F. [Auteur]
Oncovet
Pascal, Q. [Auteur]
Floch, F. [Auteur]
Geeraert, K. [Auteur]
Coste, V. [Auteur]
Marescaux, L. [Auteur]
Cagnol, S. [Auteur]
Atlanthera
Goujon, J. Y. [Auteur]
Egorov, M. [Auteur]
Le Bot, R. [Auteur]
Tierny, Dominique [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Journal title :
Oncotarget
Abbreviated title :
Oncotarget
Volume number :
11
Pages :
4281-4292
Publication date :
2021-04-23
ISSN :
1949-2553
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Purpose: 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 ...
Show more >Purpose: 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. Experimental Design: 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 (n = 1), 6 mg/kg (n = 2), 8 mg/kg (n = 3), and 10 mg/kg (n = 4). Endpoints included safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity (DLT). Results: The MTD of 12b80 was 8 mg/kg (i.e., equivalent dose of doxorubicin of 110 mg/m2, range: 93–126). Most adverse events included grade ≤ 2 gastrointestinal disorders and hypersensitivity reactions. No hematological or cardiac DLT were observed at any dose tested. Conclusions: In dogs, 12b80 is overall well tolerated and expends the MTD of doxorubicin up to four times the standard dose of 30 mg/m2. These results demonstrate the potential therapeutic benefit of 12b80 in canine and human osteosarcoma.Show less >
Show more >Purpose: 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. Experimental Design: 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 (n = 1), 6 mg/kg (n = 2), 8 mg/kg (n = 3), and 10 mg/kg (n = 4). Endpoints included safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity (DLT). Results: The MTD of 12b80 was 8 mg/kg (i.e., equivalent dose of doxorubicin of 110 mg/m2, range: 93–126). Most adverse events included grade ≤ 2 gastrointestinal disorders and hypersensitivity reactions. No hematological or cardiac DLT were observed at any dose tested. Conclusions: In dogs, 12b80 is overall well tolerated and expends the MTD of doxorubicin up to four times the standard dose of 30 mg/m2. These results demonstrate the potential therapeutic benefit of 12b80 in canine and human osteosarcoma.Show less >
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Submission date :
2023-12-13T05:11:18Z
2024-01-23T16:24:13Z
2024-01-23T16:24:13Z
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