Phase I trial of fludarabine, bortezomib and rituximab for relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma

被引:23
作者
Barr, Paul M. [1 ]
Fu, Pingfu [2 ]
Lazarus, Hillard M. [1 ]
Horvath, Nancy [1 ]
Gerson, Stanton L. [1 ]
Koc, Omer N. [3 ]
Bahlis, Nizar J. [4 ]
Snell, Michael R. [5 ]
Dowlati, Afshin [1 ]
Cooper, Brenda W. [1 ]
机构
[1] Univ Hosp Cleveland, Case Med Ctr, Case Comprehens Canc Ctr, Dept Med, Cleveland, OH 44106 USA
[2] Univ Hosp Cleveland, Case Med Ctr, Case Comprehens Canc Ctr, Dept Biostat & Epidemiol, Cleveland, OH 44106 USA
[3] Cleveland Clin, Dept Med, Cleveland, OH 44106 USA
[4] Univ Calgary, Dept Med, Calgary, AB, Canada
[5] Metrohlth Med Ctr, Dept Med, Cleveland, OH USA
基金
美国国家卫生研究院;
关键词
non-Hodgkin lymphoma; bortezomib; proteasome; fludarabine; rituximab; PROTEASOME INHIBITOR BORTEZOMIB; CHRONIC LYMPHOCYTIC-LEUKEMIA; LATE-ONSET NEUTROPENIA; NATIONAL-CANCER-INSTITUTE; LOW-GRADE; COMBINATION; VITRO; CHEMOTHERAPY; THERAPY; CYCLOPHOSPHAMIDE;
D O I
10.1111/j.1365-2141.2009.07836.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
P>Based on the hypothesis that bortezomib may potentiate fludarabine activity by inhibiting DNA repair, we designed a phase I trial using this combination with rituximab in patients with relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma. Twenty-four patients were enrolled. Non-Hodgkin lymphoma subtypes included 12 patients with follicular lymphoma, four with marginal zone lymphoma, three with lymphoplasmacytic lymphoma, three with mantle cell lymphoma and two with small lymphocytic/chronic lymphocytic leukaemia. Fludarabine and bortezomib were escalated in cohorts of three patients. Rituximab was added to the maximum tolerated dose of fludarabine and bortezomib and added significant dose-limiting myelosuppression. The maximum tolerated dose was fludarabine 25 mg/m<SU2</SU on days 1-3, bortezomib 1 center dot 3 mg/m<SU2</SU on days 1, 4, 8, 11, with rituximab 375 mg/m<SU2</SU on day 1 administered every 21 d. Clinical responses were observed in 11 patients, five of whom were refractory to their most recent treatment regimen. Six additional patients had stable disease for a median of 10 months (range 4-30+). Cumulative myelosuppression and neuropathy was observed. The combination of fludarabine, bortezomib, and rituximab appears to be an active regimen with manageable toxicity for relapsed NHL.
引用
收藏
页码:89 / 96
页数:8
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