A Phase 2 Study of Epothilone B Analog BMS-247550 (NSC 710428) in Patients With Relapsed Aggressive Non-Hodgkin Lymphomas

作者：Churpek Jane E; Pro Barbara; van Besien Koen; Kline Justin; Conner Kathy; Wade James L III; Hagemeister Fredrick; Karrison Theodore; Smith Sonali M^*

来源：Cancer, 2013, 119(9): 1683-1689.

DOI：10.1002/cncr.27917

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

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. Cancer 2013; 119: 1683-9.

• 出版日期2013-5-1