vorinostat + bortezomib

The combination of vorinostat and bortezomib is a therapeutic regimen that has been studied in various clinical trials for the treatment of multiple myeloma and glioblastoma. Based on the search results, I can provide comprehensive information about this drug combination. ## Mechanism and Clinical Development Vorinostat is a histone deacetylase (HDAC) inhibitor that has shown evidence of single-agent activity in glioblastoma. When combined with bortezomib, a proteasome inhibitor, preclinical studies demonstrated significant synergistic cytotoxicity in glioblastoma cell lines and enhanced cell death in multiple myeloma[1][2]. The combination has been evaluated in several clinical trials: - A Phase I trial determined that the maximum tolerated dose (MTD) of vorinostat was 400 mg daily for 8 days every 21 days, with bortezomib administered at 1.3 mg/m² on days 1, 4, 8, and 11[2]. - A Phase III study (VANTAGE 088) in patients with progressive multiple myeloma showed a 23% reduction in the risk of progression compared to bortezomib alone, meeting its primary endpoint[6]. However, the clinical relevance of this difference (only 0.8 months improvement in progression-free survival) has been questioned[7]. - A Phase II trial in recurrent glioblastoma was closed at the predetermined interim analysis with 0 of 34 patients being progression-free at 6 months. The median time to progression was 1.5 months, and median overall survival was 3.2 months[1]. ## Safety Profile The combination therapy has shown some notable adverse effects: - In the Phase III study, significantly more patients treated with the combination experienced thrombocytopenia (55% vs. 33%), diarrhea (62% vs. 43%), nausea (61% vs. 39%), vomiting (45% vs. 26%), and fatigue (40% vs. 31%) compared to bortezomib alone[6]. - In the glioblastoma Phase II trial, grade 3-4 nonhematologic toxicity occurred in 30% of patients (mainly fatigue at 14% and neuropathy at 5%), while grade 3-4 hematologic toxicity occurred in 37% of patients (primarily thrombocytopenia at 30%)[1]. Despite these challenges, the promising anti-myeloma activity of the regimen in refractory patients has been noted as meriting further evaluation, particularly for multiple myeloma[2].

Brand names

ZolinzaVelcade

Other names

vorinostat and bortezomib combinationZolinza and Velcade combination