Abstract
Background: Patients with Hodgkin’s Lymphoma with relapse or refractory disease after salvage therapy and transplant face a paucity of active agents. New modalities of treatment are necessary. Vorinostat (SAHA) is an orally administered hydroxamic acid histone deacetylase inhibitor with activity against class I and II deactylases. After initial phase I data (Kelley WK, et al 2005) showed prolonged stable disease in patients with Hodgkin’s, a Phase II study of this agent was launched in patients with relapsed or refractory Hodgkin’s lymphoma.
Methods: Eligible patients had relapsed or refractory Hodgkin’s lymphoma, bidimensionally measurable disease, and performance status 0-2. Patients may have received up to five prior chemotherapy regimens; previous autologous transplant is allowed. Vorinostat was dosed at 200 mg po twice daily for 14 consecutive days on a 21 day cycle. CT scanning was performed after every three cycles, as was marrow biopsy for those with marrow involvement at time of entry into study. This was a 2-stage design with a maximum planned accrual of 35 eligible patients. Objective response was the primary endpoint.
Results: Of 27 patients accrued to the first stage of this study, 25 are eligible (14 males, 11 females). Median age is 41 (19–71) years. Toxicities attributable to drug of grade 3 or higher include fatigue, anorexia, anemia, and thrombocytopenia. One partial response was observed, for a response probability of 4% (95% CI: 0%, 20%). Although there were not adequate responses to open the second stage of accrual, four patients had stable disease lasting at least one year. Of these four, one opted for radiation at 12 months, another progressed at 14 months, whereas two continue on treatment, one with bulky disease who is stable at 12 months, one with symptomatic lung involvement and bulky disease who remains stable at 16 months. One additional patient remains on treatment with stable disease at 9 months.
Conclusions: Although the low response rate led to closure of this trial after the first stage of accrual, we observed that treatment with the oral histone deacetylase inhibitor Vorinostat can lead to protracted stable disease in patients with relapsed/refractory Hodgkin’s Lymphoma. Studies in combination with other molecular agents or chemotherapy may be warranted.
A phase II study of SB939, a novel pan-histone deacetylase inhibitor, in patients with translocation-associated recurrent/metastatic sarcomas—NCIC-CTG IND 200