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A phase 2 study of epothilone B analog BMS-247550 (NSC 710428) in patients with relapsed aggressive non-Hodgkin
Jane E Churpek1, Barbara Pro, Koen van Besien
1Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, Illinois 60637, USA.
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.
Insights
Ixabepilone showed modest activity in patients with relapsed aggressive lymphomas, achieving responses in 27% of chemosensitive cases. The drug was generally well-tolerated, with manageable side effects like neutropenia and neuropathy.
Area of Science:
- Hematology
- Oncology
- Clinical Pharmacology
Background:
- Management of relapsed aggressive lymphomas presents significant challenges.
- Ixabepilone, an epothilone B analog, inhibits tubulin disassembly and shows preclinical promise in resistant cancers.
Purpose of the Study:
- To evaluate the activity and safety of ixabepilone in patients with relapsed or refractory aggressive lymphoma.
- To assess response rates in both chemosensitive and chemoresistant disease populations.
Main Methods:
- A multicenter phase 2 clinical trial administered ixabepilone at 20 mg/m(2) weekly.
- Patients received treatment on days 1, 8, and 15 of a 28-day cycle.
- Inclusion criteria specified relapsed/refractory aggressive lymphoma, categorized by chemosensitivity.
Main Results:
- Fifty-one heavily pretreated patients were enrolled, with diffuse large B-cell lymphoma being the most common histology.
- The overall response rate was 27% (12% complete response, 16% partial response), observed exclusively in chemosensitive disease.
- Median time to response was 2 cycles, with a median response duration of 9.7 months.
Conclusions:
- Ixabepilone demonstrated modest single-agent activity in recurrent, chemosensitive aggressive lymphomas.
- The drug was well-tolerated, with primary toxicities including neutropenia, peripheral neuropathy, fatigue, and nausea.
- Further investigation may be warranted for specific patient subgroups.
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