volasertib and Feeding-and-Eating-Disorders

Polo-like kinase 1 (PLK1) regulates mitotic checkpoints and cell division. PLK1 overexpression is reported in numerous cancers, including acute myeloid leukemia (AML), and is associated with poor prognosis. Volasertib is a selective, potent cell-cycle kinase inhibitor that targets PLK to induce mitotic arrest and apoptosis. This phase 1 trial investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, and anti-leukemic activity of volasertib in combination with decitabine in AML patients aged ≥ 65 years. Thirteen patients were treated with escalating volasertib doses (3 + 3 design; 300 mg, 350 mg, and 400 mg) plus standard-dose decitabine. Dose-limiting toxicity was reported in one patient in cycle 1; the MTD of volasertib in combination with decitabine was determined as 400 mg. The most common treatment-emergent adverse events were febrile neutropenia, pneumonia, and decreased appetite. Objective response rate was 23%. The combination was well tolerated, and the adverse event profile was in line with previous findings.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cell Cycle Proteins; Decitabine; Dose-Response Relationship, Drug; Febrile Neutropenia; Feeding and Eating Disorders; Female; Gene Expression; Humans; Leukemia, Myeloid, Acute; Male; Molecular Targeted Therapy; Polo-Like Kinase 1; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Pteridines; Treatment Outcome