Treatment of Glioblastoma Multiforme

Henson, John W.

doi:10.1001/archneur.63.3.337

Cited by 49 publications

(38 citation statements)

References 7 publications

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“…We describe here the preclinical characterization of ABT-414, including the assessment of activity in cell line-derived and patient-derived xenograft (PDX) models expressing either wild-type EGFR or EGFRvIII. The ability to target wildtype EGFR-and EGFRvIII-expressing tumors makes ABT-414 an attractive therapeutic candidate to treat solid tumors, including glioblastoma multiforme, where novel treatments are urgently needed (18,19). The results presented here support further clinical development of ABT-414, which is currently in ongoing phase I/II trials, where objective responses (OR) in glioblastoma multiforme patients have been observed (20).…”

Section: Introductionmentioning

confidence: 53%

ABT-414, an Antibody–Drug Conjugate Targeting a Tumor-Selective EGFR Epitope

Phillips

Boghaert

Vaidya

et al. 2016

Molecular Cancer Therapeutics

162

121

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Targeting tumor-overexpressed EGFR with an antibody-drug conjugate (ADC) is an attractive therapeutic strategy; however, normal tissue expression represents a significant toxicity risk. The anti-EGFR antibody ABT-806 targets a unique tumor-specific epitope and exhibits minimal reactivity to EGFR in normal tissue, suggesting its suitability for the development of an ADC. We describe the binding properties and preclinical activity of ABT-414, an ABT-806 monomethyl auristatin F conjugate. In vitro, ABT-414 selectively kills tumor cells overexpressing wild-type or mutant forms of EGFR. ABT-414 inhibits the growth of xenograft tumors with high EGFR expression and causes complete regressions and cures in the most sensitive models. Tumor growth inhibition is also observed in tumor models with EGFR mutations, including activating mutations and those with the exon 2-7 deletion [EGFR variant III (EGFRvIII)], commonly found in glioblastoma multiforme. ABT-414 exhibits potent cytotoxicity against glioblastoma multiforme patient-derived xenograft models expressing either wild-type EGFR or EGFRvIII, with sustained regressions and cures observed at clinically relevant doses. ABT-414 also combines with standard-of-care treatment of radiation and temozolomide, providing significant therapeutic benefit in a glioblastoma multiforme xenograft model. On the basis of these results, ABT-414 has advanced to phase I/II clinical trials, and objective responses have been observed in patients with both amplified wild-type and EGFRvIII-expressing tumors. Mol Cancer Ther; 15(4);

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Section: Introductionmentioning

confidence: 53%

ABT-414, an Antibody–Drug Conjugate Targeting a Tumor-Selective EGFR Epitope

Phillips

Boghaert

Vaidya

et al. 2016

Molecular Cancer Therapeutics

162

121

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“…Surgery and RT are still considered the basic treatment, and can be complemented with chemotherapy [1][2][3][4]6,13,[15][16][17][18][19][20]. The present investigation revealed that survival time of patients from group 2 (11.9 months) was statistically superior to that of patients from group 1 (7.4 months).…”

Section: Discussionmentioning

confidence: 58%

Effects of Socioeconomic on Survival for Adult Glioblastoma Multiform Patients in Rio de Janeiro, Brazil, 1999-2009

Lynch¹,

Welling²,

Escosteguy³

et al. 2012

OJMN

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Backgrond: To compare the survival of glioblastoma multiforme (GBM) patients operated on at public hospital with that of patients operated on at the private hospital. Method: We carried out a retrospective analysis of the patients' medical records, the surgical reports, and the pre and post-operative images of patients with a histopathological confirmed adult supratentorial glioblastoma multiform (GBM). Sixty-three patients were treated at public hospital and 21 at private hospitals. Results: The present study revealed that the survival of patients treated in private hospitals was statistically superior to that of patients treated in public hospitals (11.9 vs 7.7). Conclusions: Our study advances towards the confirmation of the hypothesis that socioeconomic and educational factors influence the KPS and the performance of RT treatment, with negative effects over the GBM patients' survival.

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“…Drug administration by the IV or oral routes is routinely used to treat GBM patients [22]. Our results show that IV administration leads to a modest accumulation of all five platinum drugs tested in the F98 tumor implanted in brain of Fischer rats.…”

Section: Discussionmentioning

confidence: 69%

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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Treatment of Glioblastoma Multiforme

Cited by 49 publications

References 7 publications

ABT-414, an Antibody–Drug Conjugate Targeting a Tumor-Selective EGFR Epitope

ABT-414, an Antibody–Drug Conjugate Targeting a Tumor-Selective EGFR Epitope

Effects of Socioeconomic on Survival for Adult Glioblastoma Multiform Patients in Rio de Janeiro, Brazil, 1999-2009

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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