Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia

被引:8
作者
Allen, Steven L. [1 ]
Kolitz, Jonathan E. [2 ]
Lundberg, Ante S. [3 ]
Bennett, John M. [4 ]
Capizzi, Robert L. [3 ]
Budman, Daniel R. [2 ]
机构
[1] N Shore Univ Hosp, Albert Einstein Coll Med, Monter Canc Ctr, Lake Success, NY 11042 USA
[2] New York Univ, N Shore Univ Hosp, Monter Canc Ctr, Sch Med, Lake Success, NY USA
[3] Antisoma, Cambridge, MA USA
[4] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA
关键词
AML; Phase I; P-glycoprotein; Pgp; Multidrug resistance; SOUTHWEST-ONCOLOGY-GROUP; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; MYELODYSPLASTIC-SYNDROME; POSTREMISSION THERAPY; ANTITUMOR-ACTIVITY; ELDERLY-PATIENTS; GROUP-B; CANCER; INDUCTION;
D O I
10.1016/j.leukres.2009.07.038
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Amonafide-L-malate ( amonafide) is a unique DNA intercalator that maintains activity in the presence of MDR mechanisms, a frequent cause of treatment-failure in secondary AML. 43 patients with relapsed/refractory or secondary AML or CML blast crisis were enrolled into two phase I dose-escalation studies investigating amonafide as monotherapy or in combination with cytarabine. 3/17 patients in the monotherapy trial and 10/26 patients in the combination trial achieved a complete remission. Between both trials responses occurred in 9/20 patients with secondary AML. Both trials demonstrated an acceptable safety profile and significant antileukemic activity in patients with poor-risk AML, especially those with secondary AML. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:487 / 491
页数:5
相关论文
共 28 条
  • [1] Age and acute myeloid leukemia
    Appelbaum, FR
    Gundacker, H
    Head, DR
    Slovak, ML
    Willman, CL
    Godwin, JE
    Anderson, JE
    Petersdorf, SH
    [J]. BLOOD, 2006, 107 (09) : 3481 - 3485
  • [2] Baer Maria R, 2005, Clin Adv Hematol Oncol, V3, P910
  • [3] Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720
    Baer, MR
    George, SL
    Dodge, RK
    O'Loughlin, KL
    Minderman, H
    Caligiuri, MA
    Anastasi, J
    Powell, BL
    Kolitz, JE
    Schiffer, CA
    Bloomfield, CD
    Larson, RA
    [J]. BLOOD, 2002, 100 (04) : 1224 - 1232
  • [4] Breast cancer resistance protein and P-glycoprotein in 149 adult acute myeloid leukemias
    Benderra, Z
    Faussat, AM
    Sayada, L
    Perrot, JY
    Chaoui, D
    Marie, JP
    Legrand, O
    [J]. CLINICAL CANCER RESEARCH, 2004, 10 (23) : 7896 - 7902
  • [5] MRP3, BCRR and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia
    Benderra, Z
    Faussat, AM
    Sayada, L
    Perrot, JY
    Tang, RP
    Chaoui, D
    Morjani, H
    Marzac, C
    Marie, JP
    Legrand, O
    [J]. CLINICAL CANCER RESEARCH, 2005, 11 (21) : 7764 - 7772
  • [6] BENNETT JM, 1982, BRIT J HAEMATOL, V51, P189, DOI 10.1111/j.1365-2141.1982.tb08475.x
  • [7] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia
    Burcu, M.
    O'Loughlin, K. L.
    Ford, L. A.
    Baer, M. R.
    [J]. LEUKEMIA, 2008, 22 (11) : 2110 - 2115
  • [8] Amonafide, a topoisomerase II inhibitor, is unaffected by P-glycoprotein-mediated efflux
    Chau, MyDoanh
    Christensen, Jennifer L.
    Ajami, Alfred M.
    Capizzi, Robert L.
    [J]. LEUKEMIA RESEARCH, 2008, 32 (03) : 465 - 473
  • [9] Cripe LD, 2006, BLOOD, V108, p129A
  • [10] The role of MDR-related proteins in the prognosis of adult acute myeloid leukaemia (AML) with normal karyotype
    Damiani, Daniela
    Tiribelli, Mario
    Raspadori, Donatella
    Michelutti, Angela
    Gozzetti, Alessandro
    Calistri, Elisabetta
    Candoni, Anna
    Chiarvesio, Alexsia
    Lenoci, Mariapia
    Russo, Domenico
    Fanin, Renato
    [J]. HEMATOLOGICAL ONCOLOGY, 2007, 25 (01) : 38 - 43