Phase I trial of alisertib with concurrent fractionated stereotactic re-irradiation for recurrent high grade gliomas.
Radiother Oncol
; 132: 135-141, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30825962
ABSTRACT
BACKGROUND AND PURPOSE:
We conducted a phase I trial of alisertib, an oral aurora kinase inhibitor, with fractionated stereotactic re-irradiation therapy (FSRT) for patients with recurrent high grade glioma (HGG). MATERIALS ANDMETHODS:
Adult patients with recurrent HGG were enrolled from Feb 2015 to Feb 2017. Patients were treated with concurrent FSRT and alisertib followed by maintenance alisertib. Concurrent alisertib dose was escalated from 20â¯mg to 50â¯mg twice daily (BID).RESULTS:
17 patients were enrolled. Median follow-up was 11â¯months. Median FSRT dose was 35â¯Gy. There were 6, 6, 3, and 2 patients enrolled in 20â¯mg, 30â¯mg, 40â¯mg, and 50â¯mg cohort, respectively. Only one DLT was observed. One patient in the 20â¯mg cohort had severe headache (Grade 3) resolved with steroids. There was no non-hematological grade 3 or higher toxicity. There were two Grade 4 late toxicities (one with grade 4 neutropenia and leukopenia, one with pulmonary embolism). One patient developed radiation necrosis (Grade 3). Sixteen patients finished concurrent treatment and received maintenance therapy (median cycles was 3, range 1-9). OS for all cohorts at 6â¯months was 88.2% with median survival time of 11.1â¯months. PFS at 6â¯months was 35.3% with median time to progression of 4.9â¯months. The trial stopped early due to closure of alisertib program with only 2 of 3 planned patients enrolled in the 50â¯mg cohort.CONCLUSION:
Re-irradiation with FSRT combined with alisertib is safe and well tolerated for HGG with doses up to 40â¯mg BID. Although no DLT observed in the 50â¯mg cohort, this cohort was not fully enrolled and MTD was not reached. Clinical outcomes appear comparable to historical results. (NCT02186509).Palavras-chave
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Assunto principal:
Pirimidinas
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Azepinas
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Neoplasias Encefálicas
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Radiocirurgia
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Glioma
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article