Clinical activity of alvocidib (flavopiridol) in acute myeloid leukemia

被引：108

作者：

Zeidner, Joshua F. ^{[1
]}

Karp, Judith E. ^{[2
]}

机构：

[1] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[2] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

来源：

LEUKEMIA RESEARCH | 2015年 / 39卷 / 12期

关键词：

Alvocidib; Flavopiridol; FLAM; Acute myeloid leukemia; Cyclin dependent kinase; CDK inhibitors; DEPENDENT KINASE INHIBITOR; TIMED SEQUENTIAL THERAPY; ACUTE MYELOCYTIC-LEUKEMIA; TUMOR LYSIS SYNDROME; CELL-CYCLE ARREST; PHASE-I; CYTOSINE-ARABINOSIDE; CARCINOMA-CELLS; P-TEFB; ADULTS;

D O I：

10.1016/j.leukres.2015.10.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

There have been minimal therapeutic advancements in acute myeloid leukemia (AML) over the past 4 decades and outcomes remain unsatisfactory. Alvocidib (formerly flavopiridol) is a multi-serine threonine cyclin-dependent kinase inhibitor with demonstrable in vitro and clinical activity in AML when combined in a timed sequential chemotherapy regimen, FLAM (alvocidib followed by cytarabine continuous infusion and mitoxantrone). FLAM has been evaluated in sequential phase 1 and phase 2 studies in 149 and 256 relapsed/refractory and newly diagnosed non-favorable risk AML patients, respectively, with encouraging findings in both patient populations warranting further investigation. This review highlights the mechanism of action of alvocidib, pre-clinical studies of alvocidib in AML, and the clinical trials evaluating alvocidib alone and in combination with cytotoxic agents (FLAM) in AML. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：1312 / 1318

页数：7

共 50 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]

Bible KC, 1996, CANCER RES, V56, P4856

[3]

Risk factors for tumor lysis syndrome in patients with chronic lymphocytic leukemia treated with the cyclin-dependent kinase inhibitor, flavopiridol [J].

Blum, K. A. ;

Ruppert, A. S. ;

Woyach, J. A. ;

Jones, J. A. ;

Andritsos, L. ;

Flynn, J. M. ;

Rovin, B. ;

Villalona-Calero, M. ;

Ji, J. ;

Phelps, M. ;

Johnson, A. J. ;

Grever, M. R. ;

Byrd, J. C. .

LEUKEMIA, 2011, 25 (09) :1444-1451

[4]

Phase I clinical and pharmacokinetic study of a novel schedule of flavopiridol in relapsed or refractory acute leukemias [J].

Blum, William ;

Phelps, Mitch A. ;

Klisovic, Rebecca B. ;

Rozewski, Darlene M. ;

Ni, Wenjun ;

Albanese, Katie A. ;

Rovin, Brad ;

Kefauver, Cheryl ;

Devine, Steven M. ;

Lucas, David M. ;

Johnson, Amy ;

Schaaf, Larry J. ;

Byrd, John C. ;

Marcucci, Guido ;

Greyer, Michael R. .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2010, 95 (07) :1098-1105

[5]

Update on Antigen-Specific Immunotherapy of Acute Myeloid Leukemia [J].

Buckley, Sarah A. ;

Walter, Roland B. .

CURRENT HEMATOLOGIC MALIGNANCY REPORTS, 2015, 10 (02) :65-75

[6]

BURKE PJ, 1977, CANCER RES, V37, P2138

[7]

Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia [J].

Byrd, John C. ;

Lin, Thomas S. ;

Dalton, James T. ;

Wu, Di ;

Phelps, Mitch A. ;

Fischer, Beth ;

Moran, Mollie ;

Blum, Kristie A. ;

Rovin, Brad ;

Brooker-McEldowney, Michelle ;

Broering, Sarah ;

Schaaf, Larry J. ;

Johnson, Amy J. ;

Lucas, David M. ;

Heerema, Nyla A. ;

Lozanski, Gerard ;

Young, Donn C. ;

Suarez, Jose-Ramon ;

Colevas, A. Dimitrios ;

Grever, Michael R. .

BLOOD, 2007, 109 (02) :399-404

[8]

Carlson BA, 1996, CANCER RES, V56, P2973

[9]

Flavopiridol inhibits P-TEFb and blocks HIV-1 replication [J].

Chao, SH ;

Fujinaga, K ;

Marion, JE ;

Taube, R ;

Sausville, EA ;

Senderowicz, AM ;

Peterlin, BM ;

Price, DH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) :28345-28348

[10]

Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo [J].

Chao, SH ;

Price, DH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (34) :31793-31799

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