title: Clinical activity of alvocidib (flavopiridol) in acute myeloid leukemia.
abstract: 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.
authors.affiliation: University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States. Electronic address: Joshua_Zeidner@med.unc.edu.
authors.forename: Joshua F
authors.initials: JF
authors.lastname: Zeidner
authors.affiliation: Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Karp
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D002453:Cell Cycle / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000032:analysis / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016879:Salvage Therapy; D015275:Tumor Lysis Syndrome / Q000209:etiology
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005419:Flavonoids; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D010880:Piperidines; D047428:Protein Kinase Inhibitors; C077990:alvocidib; D018844:Cyclin-Dependent Kinases
keywords: Acute myeloid leukemia; Alvocidib; CDK inhibitors; Cyclin dependent kinase; FLAM; Flavopiridol