Final results of a phase I study of vorinostat, pegylated liposomal doxorubicin and bortezomib in relapsed or refractory multiple myeloma

Publication date: Available online 10 May 2017 Source:Clinical Lymphoma Myeloma and Leukemia Author(s): Peter M. Voorhees, Cristina Gasparetto, Dominic T. Moore, Diane Winans, Robert Z. Orlowski, David D. Hurd Deacetylase inhibitors have synergistic activity in combination with proteasome inhibitors and anthracyclines in preclinical models of multiple myeloma. We therefore evaluated the safety and efficacy of the deacetylase inhibitor vorinostat in combination with pegylated liposomal doxorubicin (PLD) and bortezomib in relapsed/refractory multiple myeloma. Thirty-two patients were treated with PLD and bortezomib in combination with escalating doses of vorinostat on days 4 – 11 or 1 – 14. The maximum tolerated dose of vorinostat was 400 mg on days 4 – 11. Neutropenia and thrombocytopenia attributable to protocol therapy were seen in 59% and 94% of patients, of which 37% and 47% were of ≥grade 3 severity, respectively. Constitutional and gastrointestinal adverse events of all grades were common, the majority of which were <grade 3 in severity. The overall response rate (≥partial response rate) was 65% and clinical benefit rate (≥minimal response rate) 74%. The overall response rate was 83%, 71% and 45% for patients with bortezomib-naïve, -sensitive and –refractory multiple myeloma, respectively. The median progression-free survival was 13.9 months and the 3-year overall survival 77%. Further evaluation of PLD, bortezomib and deacetylase inhibitor ...

Source: Clinical Lymphoma Myeloma and Leukemia - May 11, 2017 Category: Cancer & Oncology Source Type: research