Glioblastoma Treatment: Bypassing the Toxicity of Platinum Compounds by Using Liposomal Formulation and Increasing Treatment Efficiency With Concomitant Radiotherapy

Charest, Gabriel; Sanche, Léon; Fortin, David; Mathieu, David; Paquette, Benoît

doi:10.1016/j.ijrobp.2011.10.054

Cited by 39 publications

(37 citation statements)

References 15 publications

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“…The Gamma Knife was chosen because of its high precision to irradiate tumors implanted in rats. Only a single dose of radiation was delivered to rats with the Gamma Knife because it is easier to evaluate the concomitant effect of chemotherapy and radiation with a single dose as well as to compare our previous results [29,30] with those reported in the present study.…”

Section: Radiotherapy With Gamma Knifementioning

confidence: 67%

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

et al. 2015

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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 ™ -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 median survival time. However, less toxicity was observed in animals irradiated 24 h after CEDbased chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later.

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Section: Radiotherapy With Gamma Knifementioning

confidence: 67%

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

et al. 2015

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“…While the introduction of an electron-donating group (methoxy) on the phenyl ring (4def) did not induce any marked improvement of the in vitro growth inhibitory activity compared to the unsubstituted derivative 1i, the introduction of an electron-withdrawing group (cyano or nitro) (4ger) markedly increased this growth inhibitory activity ( Table 3) (Table 3). Temozolomide and cisplatin were used as reference compounds because temozolomide is currently the preferred drug used for the treatment of glioblastoma [4e7] and platinum derivatives are used to treat recurrent gliomas that relapse during temozolomide treatment [33]. Temozolomide revealed a modest in vitro antiproliferative activity on glioma cells ( Table 3).…”

Section: Growth Inhibitory Activity (Mtt Colorimetric Assay) On Gliommentioning

confidence: 99%

N-Aryl-N′-(chroman-4-yl)ureas and thioureas display in vitro anticancer activity and selectivity on apoptosis-resistant glioblastoma cells: Screening, synthesis of simplified derivatives, and structure–activity relationship analysis

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Lamoral-Theys

Tajeddine

et al. 2012

European Journal of Medicinal Chemistry

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“…Regarding the groups of animal injected IA, the drugs were infused in the right internal carotid artery in a retrograde manner via the external carotid as described by Fortin et al [16,17]. A solution of 1 ml of platinum formulation was injected over 20 min.…”

Section: Routes Of Drug Administrationmentioning

confidence: 99%

“…Brains were removed by craniotomy and promptly cut in two sections with a brain matrix (WPI, RBMA-300C, Sarasota, FL) as described elsewhere [17]. Briefly, left hemisphere (contralateral section) and tumor section were isolated and a part of the tumor section was divided for the cytoplasmic and nuclear compartments analysis.…”

Section: Platinum Drug Uptake In Tumor and Brain Tissuementioning

confidence: 99%

Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain

et al. 2013

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Treatment of glioblastoma with platinum compounds modestly improves progression-free survival and may cause toxic effects which prevent use at higher dose that would otherwise improve the antineoplastic effect. To reduce toxicity, we propose to encapsulate the platinum drug in a liposome. We have also tested three methods of drug administration (intra-venous, intra-arterial and intra-arterial combined with blood brain barrier disruption) to determine which one optimizes the tumor cell uptake, limits the toxicity and delivers the best concomitance effect with radiotherapy. Cisplatin, oxaliplatin, their respective liposomal formulations, Lipoplatin ™ and Lipoxal ™ , and carboplatin were assessed in F98 glioma, orthotopically implanted in Fischer rats. We found that the modest accumulation of drugs in tumor cells after intra-venous injection was significantly improved when the intra-arterial route was used and further increased after the transient opening of the blood brain barrier with mannitol. The liposomal formulations have largely reduced the toxicity and have allowed a better exploitation of the anti-cancer activity of platinum agent. Although the liposomes Lipoplatin ™ and Lipoxal ™ have shown a similar ability to CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript that of carboplatin, to accumulate in brain tumors, the highest additive effect with radiotherapy was obtained with carboplatin. We conclude that the intra-arterial infusion of carboplatin or Lipoxal ™ in concomitance with radiation therapy leads to the best tumor control as measured by an increase of mean survival time in Fischer rats implanted with the F98 glioma with a benefit in survival time of 13.4 and 6.5 days respectively compared to intra-venous.

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Glioblastoma Treatment: Bypassing the Toxicity of Platinum Compounds by Using Liposomal Formulation and Increasing Treatment Efficiency With Concomitant Radiotherapy

Abstract: Among the five platinum compounds tested, carboplatin showed the best increase in survival when combined with radiation for treatment of glioma implanted in Fischer rats.

Cited by 39 publications

References 15 publications

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

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

N-Aryl-N′-(chroman-4-yl)ureas and thioureas display in vitro anticancer activity and selectivity on apoptosis-resistant glioblastoma cells: Screening, synthesis of simplified derivatives, and structure–activity relationship analysis

Optimization of the route of platinum drugs administration to optimize the concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer rat brain

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