title: Phase I dose escalation trial of the novel proteasome inhibitor carfilzomib in patients with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma.
abstract: The proteasome complex degrades proteins involved in a variety of cellular processes and is a powerful therapeutic target in several malignancies. Carfilzomib is a potent proteasome inhibitor which induces rapid chronic lymphocytic leukemia (CLL) cell apoptosis in vitro. We conducted a phase I dose-escalation trial to determine the safety and tolerability of carfilzomib in relapsed/refractory CLL or small lymphocytic lymphoma (SLL). Nineteen patients were treated with carfilzomib initially at 20 mg/m(2), then escalated in four cohorts (27, 36, 45 and 56 mg/m(2)) on days 1, 2, 8, 9, 15 and 16 of 28-day cycles. Therapy was generally well tolerated, and no dose limiting toxicities were observed. The most common hematologic toxicities were thrombocytopenia and neutropenia. All patients evaluable for response had stable disease, including patients with del17p13 and fludarabine-resistant disease. This trial shows acceptable tolerability and limited preliminary efficacy of carfilzomib in CLL and SLL.
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Farrukh T
authors: FT
authors: Awan
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Joseph M
authors: JM
authors: Flynn
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Jeffrey A
authors: JA
authors: Jones
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Leslie A
authors: LA
authors: Andritsos
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Kami J
authors: KJ
authors: Maddocks
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Ellen J
authors: EJ
authors: Sass
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Margaret S
authors: MS
authors: Lucas
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Weihong
authors: W
authors: Chase
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Sharon
authors: S
authors: Waymer
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Yonghua
authors: Y
authors: Ling
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Yao
authors: Y
authors: Jiang
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Mitch A
authors: MA
authors: Phelps
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: John C
authors: JC
authors: Byrd
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: David M
authors: DM
authors: Lucas
authors: a The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors: Jennifer A
authors: JA
authors: Woyach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D061988:Proteasome Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007143:Immunoglobulin Heavy Chains; D009842:Oligopeptides; D061988:Proteasome Inhibitors; C524865:carfilzomib
keywords: Proteasome inhibitor; carfilzomib; chronic lymphocytic leukemia