A phase 2 study of epothilone B analog BMS-247550 (NSC 710428) in patients with relapsed aggressive non-Hodgkin lymphomas

Jane E. Churpek, Barbara Pro, Koen Van Besien, Justin Kline, Kathy Conner, James L. Wade, Fredrick Hagemeister, Theodore Karrison, Sonali M. Smith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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/m2 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.

Original languageEnglish (US)
Pages (from-to)1683-1689
Number of pages7
JournalCancer
Volume119
Issue number9
DOIs
StatePublished - May 1 2013

Keywords

  • aggressive
  • ixabepilone
  • non-Hodgkin lymphoma
  • refractory
  • relapsed

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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