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Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma.
Kaley, Thomas J; Panageas, Katherine S; Mellinghoff, Ingo K; Nolan, Craig; Gavrilovic, Igor T; DeAngelis, Lisa M; Abrey, Lauren E; Holland, Eric C; Lassman, Andrew B.
Afiliação
  • Kaley TJ; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. kaleyt@mskcc.org.
  • Panageas KS; The Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA. kaleyt@mskcc.org.
  • Mellinghoff IK; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Nolan C; The Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Gavrilovic IT; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • DeAngelis LM; The Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Abrey LE; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Holland EC; The Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Lassman AB; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
J Neurooncol ; 144(2): 403-407, 2019 Sep.
Article em En | MEDLINE | ID: mdl-31325145
PURPOSE: Perifosine (PRF) is an oral alkylphospholipid with antineoplastic effects and reasonable tolerability. It inhibits signaling through the PI3/AKT axis and other cascades of biologic importance in glioblastoma, and has promising pre-clinical activity in vitro and in vivo. Therefore, we conducted a phase II open-label single-arm clinical trial of perifosine for patients with recurrent glioblastoma (GBM). METHODS: We planned to accrue up to 30 adults with recurrent GBM with a minimum Karnofsky Performance Status of 50 following radiotherapy but without other restrictions on the number or types of prior therapy. Concurrent p450 stimulating hepatic enzyme inducing anticonvulsants were prohibited. Patients were treated with a loading dose of 600 mg PRF (in 4 divided doses on day 1) followed by 100 mg daily until either disease progression or intolerable toxicity. The primary endpoint was the 6-month progression free survival (PFS6) rate, with at least 20% considered promising. Accrual was continuous but if 0 of the first 12 patients with GBM reached PFS6, then further accrual would terminate for futility. Patients with other high grade gliomas were accrued concurrently to an exploratory cohort. RESULTS: Treatment was generally well tolerated; gastrointestinal toxicities were the most common side effects, although none resulted in treatment discontinuation. However, there was limited to no efficacy in GBM (n = 16): the PFS6 rate was 0%, median PFS was 1.58 months [95% CI (1.08, 1.84)], median overall survival was 3.68 months [95% CI (2.50, 7.79)], with no radiographic responses. There was a confirmed partial response in one patient with anaplastic astrocytoma (n = 14). CONCLUSIONS: PRF is tolerable but ineffective as monotherapy for GBM. Preclinical data suggests synergistic effects of PRF in combination with other approaches, and further study is ongoing.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosforilcolina / Neoplasias Encefálicas / Glioblastoma / Proteínas Proto-Oncogênicas c-akt / Recidiva Local de Neoplasia Tipo de estudo: Observational_studies / Prognostic_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosforilcolina / Neoplasias Encefálicas / Glioblastoma / Proteínas Proto-Oncogênicas c-akt / Recidiva Local de Neoplasia Tipo de estudo: Observational_studies / Prognostic_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article