Convection-enhancement delivery of platinum-based drugs and Lipoplatin(TM) to optimize the concomitant effect with radiotherapy in F98 glioma rat model

Investigational New Drugs
Minghan ShiBenoit Paquette

Abstract

The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum-based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin(TM) - liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of media...Continue Reading

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Citations

Aug 21, 2019·Journal of Oncology·Minghan Shi, Léon Sanche
Jan 19, 2018·International Journal of Molecular Medicine·Shi-Xiang YuanFang-Cheng Li
Jun 2, 2017·Molecular Cancer Therapeutics·Amanda R KingW Mark Saltzman
Apr 14, 2019·Trends in Pharmacological Sciences·Hélène LajousEmmanuel Garcion

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