A multicentre phase II clinical experience with the novel aza-epothilone Ixabepilone (BMS247550) in patients with relapsed or refractory indolent non-Hodgkin lymphoma and mantle cell lymphoma Journal Article

Authors: O'Connor, O. A.; Portlock, C.; Moskowitz, C.; Straus, D.; Hamlin, P.; Stubblefield, M.; Dumitrescu, O.; Colevas, A. D.; Grant, B.; Zelenetz, A.
Article Title: A multicentre phase II clinical experience with the novel aza-epothilone Ixabepilone (BMS247550) in patients with relapsed or refractory indolent non-Hodgkin lymphoma and mantle cell lymphoma
Abstract: The epothilones represent a novel group of microtubule stabilization agents that appear to retain activity even in chemotherapy-resistant cell lines and animal models. Because of their ability to overcome chemotherapy resistance, we conducted a phase II study of Ixabepilone in patients with indolent non-Hodgkin lymphoma and mantle cell lymphoma (MCL). Ixabepilone was given at a dose of 25 mg/m2 weekly for three of four consecutive weeks. Patients were required to have received ≤4 prior chemotherapy regimens, with an interval of at least one month since the last treatment, 3 months from prior rituximab, and 7 d from prior steroids, an absolute neutrophil count >1 × 10 9/l and a platelet count >50 × 109/l. Dose reductions were allowed. The overall response rate in assessable patients was 27% in this otherwise heavily treated population. One patient with chemotherapy-refractory follicular lymphoma attained a complete remission that lasted approximately 8 months. Three responses were also seen in refractory MCL and one in small lymphocytic lymphoma. The duration of response ranged from 2 to 8 months. Major toxicities included fatigue, myelosuppression and neuropathy. These data suggest that Ixabepilone has activity in chemotherapy-refractory lymphoma. © 2008 The Authors.
Keywords: adult; cancer chemotherapy; clinical article; treatment outcome; aged; aged, 80 and over; middle aged; fludarabine; prednisone; thalidomide; clinical trial; constipation; fatigue; neutropenia; doxorubicin; diarrhea; drug dose reduction; drug efficacy; monotherapy; antineoplastic agents; methotrexate; rituximab; carboplatin; bortezomib; mantle cell lymphoma; multiple cycle treatment; neutrophil count; phase 2 clinical trial; bone marrow suppression; etoposide; leukopenia; neuropathy; thrombocytopenia; drug administration schedule; recurrence; combination chemotherapy; alkylating agent; cyclophosphamide; dexamethasone; vincristine; ifosfamide; procarbazine; febrile neutropenia; lymphocytopenia; gastrointestinal toxicity; prednisolone; vincristine sulfate; nonhodgkin lymphoma; cancer vaccine; drug mechanism; lymphoma, non-hodgkin; multicenter study; motor neurons; sensory receptor cells; mitoxantrone; lymphoma; thrombocyte count; remission induction; cancer relapse; electromyography; maximum tolerated dose; tositumomab i 131; lymphoma, follicular; pralatrexate; chlorambucil; pentostatin; ixabepilone; epothilones; epothilone derivative; lymphoma, mantle-cell; cladribine; peginterferon; neural conduction; indolent non-hodgkin lymphoma
Journal Title: British Journal of Haematology
Volume: 143
Issue: 2
ISSN: 0007-1048
Publisher: John Wiley & Sons  
Date Published: 2008-10-01
Start Page: 201
End Page: 209
Language: English
DOI: 10.1111/j.1365-2141.2008.07271.x
PUBMED: 18691173
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 6" - "Export Date: 17 November 2011" - "CODEN: BJHEA" - "Source: Scopus"
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MSK Authors
  1. Carol Portlock
    181 Portlock
  2. Craig Moskowitz
    375 Moskowitz
  3. Andrew D Zelenetz
    556 Zelenetz
  4. Paul Hamlin
    174 Hamlin
  5. David J Straus
    213 Straus