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.
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 lymphomapatients 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.
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Authors: D R Budman; G R Petroni; J L Johnson; M R Cooper; D M Schlossman; M Barcos; B A Peterson Journal: J Clin Oncol Date: 1997-10 Impact factor: 44.544
Authors: Michael Crump; Tara Baetz; Stephen Couban; Andrew Belch; Deborah Marcellus; Kang Howson-Jan; Kevin Imrie; Robert Myers; Grenfell Adams; Keyue Ding; Nancy Paul; Lois Shepherd; Jose Iglesias; Ralph Meyer Journal: Cancer Date: 2004-10-15 Impact factor: 6.860
Authors: W H Wilson; B A Chabner; G Bryant; S Bates; A Fojo; J Regis; E S Jaffe; S M Steinberg; B R Goldspiel; B D Cheson Journal: J Clin Oncol Date: 1995-02 Impact factor: 44.544
Authors: A Younes; A Sarris; A Melnyk; J Romaguera; P McLaughlin; F Swan; M A Rodriguez; F Hagemeister; D Moore; L North Journal: J Clin Oncol Date: 1995-03 Impact factor: 44.544
Authors: David A Rizzieri; Gregory J Sand; Dean McGaughey; Joseph O Moore; Carlos DeCastro; Nelson J Chao; James J Vredenburgh; Cristina Gasparetto; Gwynn D Long; Elizabeth Anderson; Tracy Foster; Bonnie Toaso; Donna Adams; Donna Niedzwiecki; Jon P Gockerman Journal: Cancer Date: 2004-06-01 Impact factor: 6.860