Phase 1 Trial of Bortezomib Plus R-CHOP in Previously Untreated Patients With Aggressive Non-Hodgkin Lymphoma

被引:38
作者
Furman, Richard R. [2 ]
Martin, Peter [2 ]
Ruan, Jia [2 ]
Cheung, Ying-Kuen K. [3 ]
Vose, Julie M. [4 ]
LaCasce, Ann S. [5 ]
Elstrom, Rebecca [2 ]
Coleman, Morton [2 ]
Leonard, John P. [1 ,2 ]
机构
[1] Cornell Univ, Weill Cornell Med Coll, Ctr Lymphoma & Myeloma, New York, NY 10021 USA
[2] New York Presbyterian Hosp, New York, NY USA
[3] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA
[4] Univ Nebraska Med Ctr, Div Hematol Oncol, Omaha, NE USA
[5] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
关键词
bortezomib; cyclophosphamide; doxorubicin; vincristine; and prednisone (CHOP); rituximab; diffuse large B-cell lymphoma; mantle cell lymphoma; non-Hodgkin lymphoma; maximum tolerated dose; toxicity; MANTLE-CELL LYMPHOMA; PROTEASOME INHIBITOR BORTEZOMIB; I CLINICAL-TRIALS; NF-KAPPA-B; RITUXIMAB; CHEMOTHERAPY; EFFICACY; INDOLENT; THERAPY; TIME;
D O I
10.1002/cncr.25509
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: Bortezomib has preclinical and clinical in B-cell lymphomas, both alone and in combination with other agents. A phase 1 evaluation was conducted of bortezomib with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with untreated diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL). METHODS: Twenty patients (16 with DLBCL and 4 with MCL) with a median age of 66 years (range, 29-84 years) were enrolled. Eleven subjects (55%) had an elevated lactate dehydrogenase level, and 10 patients (50%) had International Prognostic Index scores of 3 to 5. Standard R-CHOP was administered on a 21-day cycle for 6 cycles, with 1 of 3 dose levels of bortezomib (0.7 mg/m(2) [n = 4 patients], 1.0 mg/m(2) [n = 9 patients], or 1.3 mg/m(2) [n = 7 patients]) administered on Days 1 and 4 of each cycle. RESULTS: The maximum tolerated dose of bortezomib with R-CHOP was not reached, and the 1.3-mg/m(2) dose level had acceptable tolerability. A dose-limiting toxicity (pulmonary) was only observed in 1 patient receiving 1.0 mg/m(2) of bortezomib. Neuropathy occurred in 13 patients (65%), but was mostly grade 1 (45%) and reached grade 3 in only 1 patient (all toxicities were graded using the Common Terminology Criteria for Adverse Events, version 3.0). Grade 4 hematologic toxicity occurred in 7 patients (35%). Of 19 evaluable patients, all responded, with 18 (95%) cases of complete response/complete response unconfirmed achieved and 1 (5%) partial response reported. At a median follow-up of 56 months, overall survival at 4 years was 75% and progression-free survival was 58%. CONCLUSIONS: Bortezomib at a dose of 1.3 mg/m(2) twice per cycle can be added to R-CHOP chemotherapy with acceptable toxicity. Multi-institutional and cooperative group follow-up studies of this regimen are currently ongoing. Cancer 2010;116:5432-9. (C) 2010 American Cancer Society.
引用
收藏
页码:5432 / 5439
页数:8
相关论文
共 41 条
[1]  
Aghajanian C, 2002, CLIN CANCER RES, V8, P2505
[2]   Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling [J].
Alizadeh, AA ;
Eisen, MB ;
Davis, RE ;
Ma, C ;
Lossos, IS ;
Rosenwald, A ;
Boldrick, JG ;
Sabet, H ;
Tran, T ;
Yu, X ;
Powell, JI ;
Yang, LM ;
Marti, GE ;
Moore, T ;
Hudson, J ;
Lu, LS ;
Lewis, DB ;
Tibshirani, R ;
Sherlock, G ;
Chan, WC ;
Greiner, TC ;
Weisenburger, DD ;
Armitage, JO ;
Warnke, R ;
Levy, R ;
Wilson, W ;
Grever, MR ;
Byrd, JC ;
Botstein, D ;
Brown, PO ;
Staudt, LM .
NATURE, 2000, 403 (6769) :503-511
[3]   A phase II study of bortezomib in mantle cell lymphoma: The National Cancer Institute of Canada Clinical Trials Group trial IND.150 [J].
Belch, A. ;
Kouroukis, C. T. ;
Crump, M. ;
Sehn, L. ;
Gascoyne, R. D. ;
Klasa, R. ;
Powers, J. ;
Wright, J. ;
Eisenhauer, E. A. .
ANNALS OF ONCOLOGY, 2007, 18 (01) :116-121
[4]   CHOP plus rituximab - Balancing facts and opinion. [J].
Cheson, BD .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (04) :280-282
[5]   Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas [J].
Cheson, BD ;
Horning, SJ ;
Coiffier, B ;
Shipp, MA ;
Fisher, RI ;
Connors, JM ;
Lister, TA ;
Vose, J ;
Grillo-López, A ;
Hagenbeek, A ;
Cabanillas, F ;
Klippensten, D ;
Hiddemann, W ;
Castellino, R ;
Harris, NL ;
Armitage, JO ;
Carter, W ;
Hoppe, R ;
Canellos, GP .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (04) :1244-1253
[6]   A simple technique to evaluate model sensitivity in the continual reassessment method [J].
Cheung, YK ;
Chappell, R .
BIOMETRICS, 2002, 58 (03) :671-674
[7]   Sequential designs for phase I clinical trials with late-onset toxicities [J].
Cheung, YK ;
Chappell, R .
BIOMETRICS, 2000, 56 (04) :1177-1182
[8]  
CHEVRET S, 1993, STAT MED, V12, P1093
[9]   State-of-the-art therapeutics: Diffuse large B-cell lymphoma [J].
Coiffier, B .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (26) :6387-6393
[10]   Treatment of non-Hodgkin's lymphoma: A look over the past decade [J].
Coiffier, Bertrand .
CLINICAL LYMPHOMA & MYELOMA, 2006, 7 :S7-S13