Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II).
J Neurooncol
; 144(2): 303-311, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31392595
ABSTRACT
BACKGROUND:
Current bevacizumab-based regimens have failed to improve survival in patients with recurrent glioblastoma. To improve treatment efficacy, we evaluated bevacizumab + BKM120, an oral pan-class I PI3K inhibitor, in this patient population.METHODS:
A brief phase I study established the optimal BKM120 dose to administer with standard-dose bevacizumab. BKM120 60 mg PO daily + bevacizumab 10 mg/kg IV every 2 weeks in 28-day cycles was then administered to patients with relapsed/refractory glioblastoma in the phase II portion.RESULTS:
Eighty-eight patients enrolled (phase I, 12; phase II, 76). In phase I, BKM120 80 mg PO daily produced dose limiting toxicity in 3 of 6 patients; a BKM120 dose of 60 mg PO daily was established as the maximum tolerated dose. In phase II, the median progression-free survival (PFS) was 4.0 months (95% CI 3.4, 5.4), PFS at 6 months was 36.5%, and the overall response rate was 26%. Forty-two patients (57%) experienced one or more serious treatment related toxicities. The most common CNS toxicities included mood alteration (17%) and confusion (12%); however, these were often difficult to classify as treatment- versus tumor-related.CONCLUSIONS:
The efficacy seen in this study is similar to the efficacy previously reported with single-agent bevacizumab. This regimen was poorly tolerated, despite the low daily dose of BKM120. Further development of this combination for the treatment of glioblastoma is not recommended.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Terapia de Salvação
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Glioblastoma
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Resistencia a Medicamentos Antineoplásicos
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Fosfatidilinositol 3-Quinases
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Recidiva Local de Neoplasia
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Neoplasias
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neurooncol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos