Annals of Oncology Advance Access published online on February 21, 2008
Annals of Oncology, doi:10.1093/annonc/mdn031
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Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma
1 Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada
2 Department of Hematology, Centre Hospitalier Lyon-Sud, Lyon, France
3 Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA
4 Department of Clinical Oncology, Merck Research Laboratories, Whitehouse Station, NJ
5 Department of Hematology/Oncology, Georgetown University Hospital, Washington, DC, USA
* Correspondence to: Dr M. Crump, Department of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Avenue, Room 5-108, Toronto, ON, Canada M5G 2M9. Tel: +1 416-946-4567; Fax: +1 416-946-4520; E-mail: michael.crump{at}uhn.on.ca
Background: Vorinostat has demonstrated activity in refractory cutaneous T-cell lymphoma. In a phase I trial, an encouraging activity in diffuse large-B-cell lymphoma (DLBCL) was noted.
Patients and methods: We carried out a phase II trial (NCT00097929 [ClinicalTrials.gov] ) of oral vorinostat 300 mg b.i.d. (14 days/3 weeks or 3 days/week) in patients with measurable, relapsed DLBCL who had received two or more systemic therapies. Response rate and duration (DOR), time to progression (TTP) and safety were assessed.
Results: Eighteen patients were enrolled (median age: 66 years; median prior therapies: 2). Seven received 300 mg b.i.d. 14 days/3 weeks, but four had grade 3 or 4 toxicity (dose-limiting toxicity, DLT). The schedule was amended to 300 mg b.i.d. 3 days/week), and none had DLT. One achieved a complete response (TtR = 85 days; DOR = >468 days) and one had stable disease (301 days). Sixteen discontinued for progressive disease; median TTP was 44 days. Median number of cycles was 2 (1 to >19). Common drug-related adverse experiences (AEs; mostly grade 1/2) were diarrhea, fatigue, nausea, anemia and vomiting. Three patients had dose reduction; none discontinued for drug-related AEs. Drug-related AE 
grade 3 included thrombocytopenia (16.7%) and asthenia (11.1%).
Conclusion: Vorinostat was well tolerated at 300 mg b.i.d. 3 days/week or 200 mg b.i.d. 14 days/3 weeks but had limited activity against relapsed DLBCL.
diffuse large-B-cell lymphoma, DLBCL, HDAC, histone deacetylase inhibitor, SAHA, suberoylanilide hydroxamic acid, vorinostat
Received for publication January 9, 2008. Accepted for publication January 15, 2008.
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