Phase II Study of Bevacizumab and Vorinostat for Patients with Recurrent World Health Organization Grade 4 Malignant Glioma
| Autor: | Eric S. Lipp, Dina Randazzo, David A. Reardon, James E. Herndon, Katherine B. Peters, Ashley Ghiaseddin, Annick Desjardins, Henry S. Friedman, Woody Massey, Frances McSherry, Alex Mannerino |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Non-Randomized Controlled Trials as Topic Bevacizumab Combination therapy Phases of clinical research Neutropenia World Health Organization 03 medical and health sciences 0302 clinical medicine Internal medicine Glioma Antineoplastic Combined Chemotherapy Protocols medicine Humans Survival rate Aged Vorinostat Leukopenia Brain Neoplasms business.industry Clinical Trial Results Middle Aged Prognosis medicine.disease Survival Rate Regimen 030104 developmental biology 030220 oncology & carcinogenesis Female Neoplasm Recurrence Local medicine.symptom business Follow-Up Studies medicine.drug |
| Zdroj: | The Oncologist |
| ISSN: | 1549-490X 1083-7159 |
| Popis: | Lessons Learned Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma. Treatment of recurrent glioblastoma remains challenging as this study and others attempt to improve progression-free survival and overall survival with BEV-containing regimens. Background Recurrent glioblastoma (GBM; World Health Organization grade 4) continues to have a very poor prognosis. Bevacizumab (BEV) has been shown to improve progression-free survival (PFS) in recurrent GBM and is approved by the U.S. Food and Drug Administration for the treatment of recurrent GBM. Combination regimens have been explored, and in this phase II nonrandomized trial, we evaluated the efficacy of BEV combined with histone deacetylase inhibitor vorinostat (VOR) in recurrent GBM. Materials and Methods In this phase II, single-center, nonrandomized study, subjects with recurrent GBM received BEV 10 mg/kg intravenously (IV) every 2 weeks combined with VOR 400 mg p.o. daily for 7 days on, 7 days off, in a 28-day cycle. The primary endpoint was 6-month PFS (PFS6). Results Forty patients with recurrent GBM were enrolled and evaluated. PFS6 was 30.0% (95% confidence interval [CI] 16.8%–44.4%). Median overall survival (OS) was 10.4 months (95% CI 7.6–12.8 months). Overall radiographic response rate was 22.5% based on 9 partial responses. The most common grade 2 and above treatment-related adverse events were lymphopenia (55%), leukopenia (45%), neutropenia (35%), and hypertension (33%). Grade 4 adverse events were leukopenia (3%), neutropenia (3%), sinus bradycardia (3%), and venous thromboembolism (3%). Two deaths occurred in this study, with one due to tumor progression and another possibly related as death not otherwise specified. Conclusion Combination treatment of BEV and VOR was well tolerated. This combination therapy for this study population did not improve PFS6 or median OS when compared with BEV monotherapy. |
| Databáze: | OpenAIRE |
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