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Phase I/II trial of vorinostat, bevacizumab, and daily temozolomide for recurrent malignant gliomas
- Source :
- Journal of Neuro-Oncology. 137:349-356
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Prognosis of recurrent glioblastoma (GBM) is poor with 6-month progression-free survival (PFS6) ranging from 9 to 48% depending on the treatment regimen and use of anti-angiogenic therapies. We sought to study vorinostat (VOR), a histone deacetylase inhibitor, in combination with bevacizumab (BEV) and daily metronomic temozolomide (TMZ) in a Phase I/II trial in recurrent high-grade gliomas (HGGs). This was a Phase I/II open-label, single-arm study in recurrent HGG patients. Phase I primary endpoint was to determine the maximum tolerated dose (MTD) of VOR with BEV and daily TMZ. Phase II primary endpoint was PFS6. Regimen was BEV 10 mg/kg iv every 2 weeks, TMZ 50 mg/m2 po daily, and VOR 200 or 400 mg po alternating 7 days on then 7 days off throughout a 28-day cycle. Phase I portion enrolled nine subjects with three receiving VOR 200 mg and 6 receiving VOR 400 mg. With no dose-limiting toxicities (DLTs) at 200 mg and one DLT (thrombocytopenia, Grade 3) at 400 mg, the MTD was 400 mg. Phase II portion enrolled 39 GBM subjects, and PFS6 was 53.8% (95% CI 37.2–67.9%). Of note, 14 subjects had received prior BEV and all had received prior 5-day TMZ. Combination therapy with VOR, BEV, and daily TMZ was well tolerated and safe. While PFS6 was not statistically improved beyond historical controls, it is important to note that this was a heavily pretreated GBM population and further consideration is warranted in a less pretreated group.
- Subjects :
- Adult
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Bevacizumab
Combination therapy
medicine.drug_class
Population
Antineoplastic Agents
03 medical and health sciences
0302 clinical medicine
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Temozolomide
medicine
Clinical endpoint
Humans
education
Vorinostat
education.field_of_study
Dose-Response Relationship, Drug
Brain Neoplasms
business.industry
Histone deacetylase inhibitor
Glioma
Middle Aged
Survival Analysis
Regimen
Treatment Outcome
030104 developmental biology
Neurology
030220 oncology & carcinogenesis
Female
Neurology (clinical)
Neoplasm Recurrence, Local
business
medicine.drug
Subjects
Details
- ISSN :
- 15737373 and 0167594X
- Volume :
- 137
- Database :
- OpenAIRE
- Journal :
- Journal of Neuro-Oncology
- Accession number :
- edsair.doi.dedup.....1450eb351b25d2f4430b3325661f5a42