Phase I dose escalation study of 12b80 (hydroxybisphosphonate linked doxorubicin) in naturally occurring osteosarcoma

Boyé, Pierre; David, Emmanuelle; Serres, François; Pascal, Quentin; Floch, Franck; Geeraert, Kévyn; Coste, Virginie; Marescaux, Laurent; Cagnol, Sébastien; Goujon, Jean-Yves; Egorov, Maxim; Bot, Ronan Le; Tierny, Dominique

doi:10.18632/oncotarget.27801

Cited by 5 publications

(1 citation statement)

References 30 publications

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“…Another group using a different promising approach with a pH-sensitive linker to form BP− doxorubicin conjugate (12b80) has demonstrated efficacy in an OS model 11 and in phase I clinical studies in canine spontaneous OS. 12 Previously, we have published the results of the phase I human clinical trial of MBC-11, providing the first clinical proof-of-concept by the demonstration of reduced skeletal tumor burden in patients with bone metastases. 13 Based on these studies, we hypothesized that this proven method of drug bone targeting may lead to a novel approach to the drug combination therapy at the site of bone lesions.…”

Section: ■ Introductionmentioning

confidence: 99%

Gemcitabine–Ibandronate Conjugate Enables the Bone-Targeted Combination Therapy in Bone Cancer: Synthesis and Efficacy in Combination with Docetaxel

et al. 2021

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Patients with cancer-induced bone disease, including primary bone cancers such as osteosarcoma (OS) and metastases from other tissues of origin, present a high unmet medical need. We present a potential therapeutic approach built upon a proven bone-targeting bisphosphonate conjugate platform with the known synergies of gemcitabine (GEM) and docetaxel (DTX). The synthesis of rationally designed GEM–IB, the conjugate of GEM-5′-phosphate with ibandronate (IB), is presented. GEM–IB as a single agent or in combination with DTX demonstrated reduced tumor burden, preservation of the bone architecture, and improved the survival in a murine model of OS. This is the first demonstration of a bone-targeting conjugate in combination with a second drug to create effective drug ratios in the bone compartment.

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Section: ■ Introductionmentioning

confidence: 99%