PURPOSE: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma. EXPERIMENTAL DESIGN: Patients with follicular lymphoma (FL), marginal zone lymphoma, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia were eligible for study. Bortezomib was given at a dose of 1.5 mg/m(2) as an i.v. push on days 1, 4, 8, and 11 of a 21-day cycle. Eligibility included the following: (a) no more than three prior therapies, (b) at least 1 month since prior chemotherapy, (c) measurable disease, and (d) an absolute neutrophil count of >1,000/microL and a platelet count >50,000/microL for the first dose of any cycle. RESULTS: Seventy-seven patients were registered, of which 69 were assessable for response based on the completion of two cycles of therapy. Subtypes included FL (59.5%), mantle cell lymphoma (52%), small lymphocytic lymphoma/chronic lymphocytic leukemia (16.2%), marginal zone lymphoma (21.6%), and one Waldenstrom's macroglobulinemia. The median number of prior therapies was three. The most common grade 3 toxicity was lymphopenia (35%) and thrombocytopenia (31%). Twenty-five patients experienced grade <or=2 sensory neuropathy (32), and 8% experienced grade 3 neurosensory toxicity. The overall response rate was 45% (40% on an intention to treat) including 10 complete remissions. Of 18 patients with FL, 9 responded with 4 complete response. The median time to treatment response for FL was 12 weeks, whereas the median time to treatment response for other subtypes of non-Hodgkin's lymphoma was only 4 weeks. CONCLUSIONS: These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response.
PURPOSE: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma. EXPERIMENTAL DESIGN:Patients with follicular lymphoma (FL), marginal zone lymphoma, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia were eligible for study. Bortezomib was given at a dose of 1.5 mg/m(2) as an i.v. push on days 1, 4, 8, and 11 of a 21-day cycle. Eligibility included the following: (a) no more than three prior therapies, (b) at least 1 month since prior chemotherapy, (c) measurable disease, and (d) an absolute neutrophil count of >1,000/microL and a platelet count >50,000/microL for the first dose of any cycle. RESULTS: Seventy-seven patients were registered, of which 69 were assessable for response based on the completion of two cycles of therapy. Subtypes included FL (59.5%), mantle cell lymphoma (52%), small lymphocytic lymphoma/chronic lymphocytic leukemia (16.2%), marginal zone lymphoma (21.6%), and one Waldenstrom's macroglobulinemia. The median number of prior therapies was three. The most common grade 3 toxicity was lymphopenia (35%) and thrombocytopenia (31%). Twenty-five patients experienced grade <or=2 sensory neuropathy (32), and 8% experienced grade 3 neurosensory toxicity. The overall response rate was 45% (40% on an intention to treat) including 10 complete remissions. Of 18 patients with FL, 9 responded with 4 complete response. The median time to treatment response for FL was 12 weeks, whereas the median time to treatment response for other subtypes of non-Hodgkin's lymphoma was only 4 weeks. CONCLUSIONS: These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response.
Authors: Marc A Weniger; Edgar G Rizzatti; Patricia Pérez-Galán; Delong Liu; Qiuyan Wang; Peter J Munson; Nalini Raghavachari; Therese White; Megan M Tweito; Kieron Dunleavy; Yihong Ye; Wyndham H Wilson; Adrian Wiestner Journal: Clin Cancer Res Date: 2011-06-28 Impact factor: 12.531
Authors: Beata Holkova; E Brent Perkins; Viswanathan Ramakrishnan; Mary Beth Tombes; Ellen Shrader; Neha Talreja; Martha D Wellons; Kevin T Hogan; G David Roodman; Domenico Coppola; Loveleen Kang; Jana Dawson; Robert K Stuart; Cody Peer; William D Figg; Sarah Kolla; Austin Doyle; John Wright; Daniel M Sullivan; John D Roberts; Steven Grant Journal: Clin Cancer Res Date: 2011-03-29 Impact factor: 12.531
Authors: Robert A Baiocchi; Lapo Alinari; Mark E Lustberg; Thomas S Lin; Pierluigi Porcu; Xiaobai Li; Jeffrey S Johnston; John C Byrd; Kristie A Blum Journal: Cancer Date: 2010-12-14 Impact factor: 6.860
Authors: John Gerecitano; Carol Portlock; Craig Moskowitz; Paul Hamlin; David Straus; Andrew D Zelenetz; Zhigang Zhang; Otilia Dumitrescu; Debra Sarasohn; Dorothy Lin; Jennifer Pappanicholaou; Barbara M Cortelli; Ellen Neylon; Rachel Hamelers; John Wright; Owen A O'Connor Journal: Br J Haematol Date: 2009-07-16 Impact factor: 6.998