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

来源：

LEUKEMIA RESEARCH | 2010年 / 34卷 / 04期

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

页码：487 / 491

页数：5

共 28 条

[1] Age and acute myeloid leukemia [J].

Appelbaum, FR ;

Gundacker, H ;

Head, DR ;

Slovak, ML ;

Willman, CL ;

Godwin, JE ;

Anderson, JE ;

Petersdorf, SH .

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 [J].

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 .

BLOOD, 2002, 100 (04) :1224-1232

[4] Breast cancer resistance protein and P-glycoprotein in 149 adult acute myeloid leukemias [J].

Benderra, Z ;

Faussat, AM ;

Sayada, L ;

Perrot, JY ;

Chaoui, D ;

Marie, JP ;

Legrand, O .

CLINICAL CANCER RESEARCH, 2004, 10 (23) :7896-7902

[5] MRP3, BCRR and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia [J].

Benderra, Z ;

Faussat, AM ;

Sayada, L ;

Perrot, JY ;

Tang, RP ;

Chaoui, D ;

Morjani, H ;

Marzac, C ;

Marie, JP ;

Legrand, O .

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 [J].

Burcu, M. ;

O'Loughlin, K. L. ;

Ford, L. A. ;

Baer, M. R. .

LEUKEMIA, 2008, 22 (11) :2110-2115

[8] Amonafide, a topoisomerase II inhibitor, is unaffected by P-glycoprotein-mediated efflux [J].

Chau, MyDoanh ;

Christensen, Jennifer L. ;

Ajami, Alfred M. ;

Capizzi, Robert L. .

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 [J].

Damiani, Daniela ;

Tiribelli, Mario ;

Raspadori, Donatella ;

Michelutti, Angela ;

Gozzetti, Alessandro ;

Calistri, Elisabetta ;

Candoni, Anna ;

Chiarvesio, Alexsia ;

Lenoci, Mariapia ;

Russo, Domenico ;

Fanin, Renato .

HEMATOLOGICAL ONCOLOGY, 2007, 25 (01) :38-43

← 1 2 3 →