title: Volasertib for the treatment of acute myeloid leukemia: a review of preclinical and clinical development.
abstract: Volasertib is a potent inhibitor of Polo-like kinase (PLK) 1 and to lesser extent also PLK2 and PLK3. PLKs are key regulators of the cell cycle and volasertib blocks cells in G2-M phase of the cell cycle. The compound has been evaluated in Phase I and II studies in acute myeloid leukemia and solid tumors. Side effects are mainly hematological. In acute myeloid leukemia (AML), a randomized Phase II study has been conducted in elderly patients unfit for intensive chemotherapy. Patients have been randomized to a combination of volarsetib and low-dose cytarabine versus low-dose cytarabine alone. Preliminary results show significantly higher rates of complete remission and of complete remission with incomplete hematological recovery in the combination versus the monotherapy arm, with 31% and 13%, respectively. Longer event-free survival was observed with the combination with 5.6 versus 2.3 months, respectively (p = 0.0237). These encouraging data supported the initiation of an international Phase III trial, which currently underway, to confirm these results. Volasertib has not yet been approved for regular clinical use.
authors.affiliation: Department of Hematology, Oncology & Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistrasse 52 D-20246, Hamburg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Janning
authors.forename: Walter
authors.initials: W
authors.lastname: Fiedler
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003711:Demyelinating Diseases; D018572:Disease-Free Survival; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011621:Pteridines / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic
chemical_list: C541363:BI 6727; D047428:Protein Kinase Inhibitors; D011621:Pteridines; D003561:Cytarabine
keywords: BI 6727; Polo-like kinase inhibition; acute myeloid leukemia; volasertib