title: A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma.
abstract: This study examines the activity and tolerability of a regimen combining vorinostat and rituximab in patients with indolent B-cell non-Hodgkin lymphoma. A total of 28 patients with newly diagnosed or relapsed/refractory follicular, marginal zone, or mantle cell lymphoma, with 4 or less prior therapies were eligible for this open-label phase II study. Oral vorinostat 200 mg was administered twice daily on days 1-14 along with 375 mg/m(2) of intravenous rituximab on day 1 of a 21-day cycle, continuing until disease progression or unacceptable toxicity. Primary end point was objective response rate, with secondary end points of progression-free survival, time to progression, duration of response, safety, and tolerability. Median follow up was 25.6 months and median number of vorinostat cycles was 11.5. Overall response rate was 46% for all patients, 67% for previously untreated, and 41% for relapsed/refractory patients. Median progression-free survival was 29.2 months for all patients, 18.8 months for previously treated patients, and not reached for untreated patients. The regimen was well tolerated over long treatment periods with the most common grade 3/4 adverse events being asymptomatic thrombosis, neutropenia, thrombocytopenia, lymphopenia, and fatigue. The vorinostat/rituximab combination exhibits activity in indolent B-cell non-Hodgkin lymphoma with an acceptable safety profile and durable responses. Re-treatment was effective in 2 of 3 relapsing responders. This phase II clinical trial was registered at clinicaltrials.gov identifier: 00720876.
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplant, City of Hope, Duarte, CA, USA rchen@coh.org.
authors.forename: Robert
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, City of Hope, Duarte, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplant, City of Hope, Duarte, CA, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Popplewell
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplant, City of Hope, Duarte, CA, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Siddiqi
authors.affiliation: Department of Biostatistics, City of Hope, Duarte, CA, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Ruel
authors.affiliation: Department of Radiology, City of Hope, Duarte, CA, USA.
authors.forename: Arnold
authors.initials: A
authors.lastname: Rotter
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplant, City of Hope, Duarte, CA, USA.
authors.forename: Sandra H
authors.initials: SH
authors.lastname: Thomas
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplant, City of Hope, Duarte, CA, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Mott
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplant, City of Hope, Duarte, CA, USA.
authors.forename: Nitya
authors.initials: N
authors.lastname: Nathwani
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplant, City of Hope, Duarte, CA, USA.
authors.forename: Myo
authors.initials: M
authors.lastname: Htut
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplant, City of Hope, Duarte, CA, USA.
authors.forename: Auayporn
authors.initials: A
authors.lastname: Nademanee
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplant, City of Hope, Duarte, CA, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplant, City of Hope, Duarte, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Kirschbaum
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D007275:Injections, Intravenous; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008231:Lymphopenia / Q000139:chemically induced / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D000069283:Rituximab; D016019:Survival Analysis; D013927:Thrombosis / Q000139:chemically induced / Q000473:pathology; D000077337:Vorinostat
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000069283:Rituximab; D000077337:Vorinostat