title: A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma.
abstract: A phase 1 study was conducted to determine the dose-limiting toxicities and maximum-tolerated dose (MTD) for bortezomib followed by romidepsin on days 1, 8, and 15 in patients with relapsed/refractory CLL/SLL or B- or T-cell lymphoma. Eighteen treated patients were evaluable for response. The MTD was 1.3 mg/m2bortezomib and 10 mg/m2romidepsin; median treatment duration was 3 cycles at this dose. The dose-limiting toxicities were grade 3 fatigue, vomiting, and chills. Two patients had partial responses, one lasting >2 years, 8 had stable disease, and 8 had progressive disease. The median duration of stable disease was 3.5 cycles. Correlative studies examining expression of NF-кB, XIAP, Bcl-xL, and Bim yielded variable results. The safety profile was consistent with that reported for single-agent bortezomib and romidepsin. This regimen has modest activity in heavily pretreated patients with relapsed/refractory CLL or B- or T-cell lymphoma. NCT00963274.
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.|b Department of Internal Medicine , Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Holkova
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.|b Department of Internal Medicine , Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Yazbeck
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kmieciak
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Prithviraj
authors.initials: P
authors.lastname: Bose
authors.affiliation: c Division of Hematology and Oncology , Robert H. Lurie Comprehensive Cancer Center, Northwestern University , Chicago , IL , USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Ma
authors.affiliation: d Marlene and Stewart Greenebaum Cancer Center, University of Maryland , Baltimore , MD , USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Kimball
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Tombes
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Shrader
authors.affiliation: e Department of Statistics , Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Wan
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Caryn
authors.initials: C
authors.lastname: Weir-Wiggins
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Singh
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Hogan
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Conine
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Sankala
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Roberts
authors.affiliation: f Department of Hematology/Oncology , Lineberger Comprehensive Cancer Center, University of North Carolina , Chapel Hill , NC , USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Shea
authors.affiliation: a Massey Cancer Center, Virginia Commonwealth University , Richmond , VA , USA.|b Department of Internal Medicine , Virginia Commonwealth University , Richmond , VA , USA.|g Department of Microbiology and Immunology , Virginia Commonwealth University , Richmond , VA , USA.|h Department of Biochemistry and Molecular Biology , Virginia Commonwealth University , Richmond , VA , USA.|i The Institute for Molecular Medicine, Virginia Commonwealth University , Richmond , VA , USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Grant
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage; D003131:Combined Modality Therapy; D047630:Depsipeptides / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy*; D016410:Lymphoma, T-Cell, Cutaneous / Q000175:diagnosis / Q000188:drug therapy*; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D016896:Treatment Outcome
chemical_list: D047630:Depsipeptides; D000069286:Bortezomib; C087123:romidepsin
keywords: Bortezomib; lymphoma; phase 1 clinical trial; romidepsin