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/m(2) weekly for three of four consecutive weeks. Patients were required to have received < or =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 x 10(9)/l and a platelet count >50 x 10(9)/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.
authors.affiliation: Department of Medicine, Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, Lymphoma Service, New York, NY 10032, USA. oo2130@columbia.edu
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
authors.forename: Carol
authors.initials: C
authors.lastname: Portlock
authors.forename: Craig
authors.initials: C
authors.lastname: Moskowitz
authors.forename: David
authors.initials: D
authors.lastname: Straus
authors.forename: Paul
authors.initials: P
authors.lastname: Hamlin
authors.forename: Michael
authors.initials: M
authors.lastname: Stubblefield
authors.forename: Otila
authors.initials: O
authors.lastname: Dumetrescu
authors.forename: A Dimitrios
authors.initials: AD
authors.lastname: Colevas
authors.forename: Barbara
authors.initials: B
authors.lastname: Grant
authors.forename: Andrew
authors.initials: A
authors.lastname: Zelenetz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004576:Electromyography; D034261:Epothilones / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons; D009431:Neural Conduction; D012008:Recurrence; D012074:Remission Induction; D011984:Sensory Receptor Cells; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone