Bortezomib Added to Daunorubicin and Cytarabine During Induction Therapy and to Intermediate-Dose Cytarabine for Consolidation in Patients With Previously Untreated Acute Myeloid Leukemia Age 60 to 75 Years: CALGB (Alliance) Study 10502

被引:90
作者
Attar, Eyal C. [1 ]
Johnson, Jeffrey L. [3 ]
Amrein, Philip C. [1 ]
Lozanski, Gerard [6 ]
Wadleigh, Martha [2 ]
DeAngelo, Daniel J. [2 ]
Kolitz, Jonathan E. [7 ]
Powell, Bayard L. [4 ]
Voorhees, Peter [5 ]
Wang, Eunice S. [8 ]
Blum, William [6 ]
Stone, Richard M. [2 ]
Marcucci, Guido [6 ]
Bloomfield, Clara D. [6 ]
Moser, Barry [3 ]
Larson, Richard A. [9 ,10 ]
机构
[1] Massachusetts Gen Hosp, Boston, MA 02114 USA
[2] Dana Farber Canc Inst, Boston, MA 02115 USA
[3] Duke Univ, Med Ctr, Durham, NC 27706 USA
[4] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27109 USA
[5] Univ N Carolina, Chapel Hill, NC USA
[6] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA
[7] Hofstra North Shore LIJ Sch Med, Lake Success, NY USA
[8] Roswell Pk Canc Inst, Buffalo, NY 14263 USA
[9] Univ Chicago, Chicago, IL 60637 USA
[10] Canc & Leukemia Grp B, Chicago, IL USA
基金
美国国家卫生研究院;
关键词
ACUTE MYELOGENOUS LEUKEMIA; FACTOR-KAPPA-B; CELLS; AML; ESCALATION; EXPRESSION; APOPTOSIS; REGIMEN; CANCER; TRIAL;
D O I
10.1200/JCO.2012.45.2177
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with consolidation chemotherapy consisting of intermediate-dose cytarabine (Int-DAC). Patients and Methods Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m(2) intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m2 on days 1 through 3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1 through 7. Patients who achieved complete remission (CR) received up to two courses of consolidation chemotherapy with cytarabine 2 gm/m(2) on days 1 through 5 with bortezomib. Three cohorts with escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m(2)). Dose-limiting toxicities were assessed during the first cycle of consolidation. The relationship between cell surface expression of CD74 and clinical outcome was assessed. Results Frequency of CR was 65% (62 of 95), and 4% of patients (four of 95) achieved CR with incomplete platelet recovery (CRp). Eleven patients developed grade 3 sensory neuropathy. Bortezomib plus Int-DAC proved tolerable at the highest dose tested. Lower CD74 expression was associated with CR/CRp (P = .04) but not with disease-free or overall survival. Conclusion The addition of bortezomib to standard 3 + 7 daunorubicin and cytarabine induction chemotherapy for AML resulted in an encouraging remission rate. The maximum tested dose of bortezomib administered in combination with Int-DAC for remission consolidation was 1.3 mg/m2 and proved tolerable. Further testing of this regimen is planned. J Clin Oncol 31:923-929. (C) 2012 by American Society of Clinical Oncology
引用
收藏
页码:923 / 929
页数:7
相关论文
共 20 条
[1]  
Adams J, 1999, CANCER RES, V59, P2615
[2]   Phase I and pharmacokinetic study of bortezomib in combination with idarubicin and cytarabine in patients with acute myelogenous leukemia [J].
Attar, Eyal C. ;
De Angelo, Daniel J. ;
Supko, Jeffrey G. ;
D'Amato, Ferdinando ;
Zahrieh, David ;
Sirulnik, Andres ;
Wadleigh, Martha ;
Ballen, Karen K. ;
McAfee, Steve ;
Miller, Kenneth B. ;
Levine, James ;
Galinsky, Ilene ;
Trehu, Elizabeth G. ;
Schenkein, David ;
Neuberg, Donna ;
Stone, Richard M. ;
Amrein, Philip C. .
CLINICAL CANCER RESEARCH, 2008, 14 (05) :1446-1454
[3]  
Attar EC, 2009, BLOOD, V114, P645
[4]   Escalation of daunorubicin and addition of etoposide in the ADE regimen in acute myeloid leukemia patients aged 60 years and older: Cancer and Leukemia Group B Study 9720 [J].
Baer, M. R. ;
George, S. L. ;
Sanford, B. L. ;
Mrozek, K. ;
Kolitz, J. E. ;
Moore, J. O. ;
Stone, R. M. ;
Powell, B. L. ;
Caligiuri, M. A. ;
Bloomfield, C. D. ;
Larson, R. A. .
LEUKEMIA, 2011, 25 (05) :800-807
[5]   Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemia [J].
Blum, William ;
Schwind, Sebastian ;
Tarighat, Somayeh S. ;
Geyer, Susan ;
Eisfeld, Ann-Kathrin ;
Whitman, Susan ;
Walker, Alison ;
Klisovic, Rebecca ;
Byrd, John C. ;
Santhanam, Ramasamy ;
Wang, Hongyan ;
Curfman, John P. ;
Devine, Steven M. ;
Jacob, Samson ;
Garr, Celia ;
Kefauver, Cheryl ;
Perrotti, Danilo ;
Chan, Kenneth K. ;
Bloomfield, Clara D. ;
Caligiuri, Michael A. ;
Grever, Michael R. ;
Garzon, Ramiro ;
Marcucci, Guido .
BLOOD, 2012, 119 (25) :6025-6031
[6]  
BRACH MA, 1992, MOL PHARMACOL, V41, P60
[7]   Induction therapy of AML with ara-C plus daunorubicin versus ara-C plus gemtuzumab ozogamicin: a randomized phase II trial in elderly patients [J].
Brunnberg, U. ;
Mohr, M. ;
Noppeney, R. ;
Duerk, H. A. ;
Sauerland, M. C. ;
Mueller-Tidow, C. ;
Krug, U. ;
Koschmieder, S. ;
Kessler, T. ;
Mesters, R. M. ;
Schulz, C. ;
Kosch, M. ;
Buechner, T. ;
Ehninger, G. ;
Duehrsen, U. ;
Serve, H. ;
Berdel, W. E. .
ANNALS OF ONCOLOGY, 2012, 23 (04) :990-996
[8]   The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial [J].
Burnett, Alan K. ;
Milligan, Donald ;
Goldstone, Anthony ;
Prentice, Archibald ;
McMullin, Mary-Frances ;
Dennis, Michael ;
Sellwood, Elizabeth ;
Pallis, Monica ;
Russell, Nigel ;
Hills, Robert K. ;
Wheatley, Keith .
BRITISH JOURNAL OF HAEMATOLOGY, 2009, 145 (03) :318-332
[9]   Randomized comparison of double induction and timed-sequential induction to a "3+7" induction in adults with AML:: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study [J].
Castaigne, S ;
Chevret, S ;
Archimbaud, E ;
Fenaux, P ;
Bordessoule, D ;
Tilly, H ;
de Revel, T ;
Simon, M ;
Dupriez, B ;
Renoux, M ;
Janvier, M ;
Micléa, JM ;
Thomas, X ;
Bastard, C ;
Preudhomme, C ;
Bauters, F ;
Degos, L ;
Dombret, H .
BLOOD, 2004, 104 (08) :2467-2474
[10]   Class II-associated invariant chain peptide expression on myeloid leukemic blasts predicts poor clinical outcome [J].
Chamuleau, MED ;
Souwer, Y ;
van Ham, SM ;
Zevenbergen, A ;
Westers, TM ;
Berkhof, J ;
Meijer, CJLM ;
van de Loosdrecht, AA ;
Ossenkoppele, GJ .
CANCER RESEARCH, 2004, 64 (16) :5546-5550