title: A phase 2 study of epothilone B analog BMS-247550 (NSC 710428) in patients with relapsed aggressive non-Hodgkin lymphomas.
abstract: BACKGROUND
  The management of relapsed aggressive lymphomas remains problematic. Ixabepilone (BMS-247550, epothilone B analog), a potent inhibitor of tubulin disassembly, has promising preclinical and early-phase clinical activity in drug-resistant malignancies.
  
  
  METHODS
  This multicenter phase 2 clinical trial tested the activity and safety of ixabepilone in relapsed/refractory aggressive lymphoma patients with either chemosensitive (at least a partial response [PR] to most recent chemotherapy) or chemoresistant (less than PR to most recent chemotherapy) disease at 20 mg/m(2) given intravenously weekly on days 1, 8, and 15 of a 28-day cycle.
  
  
  RESULTS
  Fifty-one enrolled patients with a median age of 66 years received at least 1 dose of ixabepilone. Diffuse large B-cell lymphoma (n = 25; 49%), mantle cell lymphoma (n = 16; 31%), and transformed follicular lymphoma (n = 5; 10%) were the most frequent histologies. Patients were heavily pretreated, with more than one-quarter having received 4 or more prior therapies. The overall response rate was 27% (14 of 51 patients) with 12% (6 patients) experiencing complete responses and 16% (8 patients) with PRs. All responses were in patients with chemosensitive disease. The median time to response was 2 cycles with a median duration of response of 9.7 months.
  
  
  CONCLUSIONS
  Ixabepilone was well-tolerated, with neutropenia, peripheral sensory neuropathy, fatigue, and nausea as the major toxicities. Ixabepilone has modest single-agent activity in patients with recurrent chemosensitive aggressive lymphomas.
authors: Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, Illinois 60637, USA.
authors: Jane E
authors: JE
authors: Churpek
authors: Barbara
authors: B
authors: Pro
authors: Koen
authors: K
authors: van Besien
authors: Justin
authors: J
authors: Kline
authors: Kathy
authors: K
authors: Conner
authors: James L
authors: JL
authors: Wade
authors: Fredrick
authors: F
authors: Hagemeister
authors: Theodore
authors: T
authors: Karrison
authors: Sonali M
authors: SM
authors: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D034261:Epothilones / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone