title: A phase II study of AZD2171 (cediranib) in the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndrome.
abstract: Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) not fit for intensive treatment need novel therapy options. Vascular endothelial growth factor (VEGF) receptor inhibition is one potential mechanism by which AML and MDS could be treated. The receptor tyrosine kinase inhibitor AZD2171 (cediranib) has activity against VEGF receptors KDR and FLT-1. This multicenter phase II study was designed to test cediranib's activity in patients with AML or high-risk MDS. The primary endpoint was confirmed disease response defined as a composite of complete remission, partial remission or hematologic improvement. The study enrolled 23 subjects in the AML cohort and 16 subjects in the MDS cohort. There were no confirmed responses in either group. Since the study met the stopping rule after the first stage of enrollment, the trial was closed to further accrual. Common adverse events in both cohorts included thrombocytopenia, neutropenia, anemia, fatigue, dyspnea, diarrhea, nausea and dehydration.
authors.affiliation: Carbone Comprehensive Cancer Center, University of Wisconsin , Madison, WI , USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Mattison
authors.forename: Alcee
authors.initials: A
authors.lastname: Jumonville
authors.forename: Patrick James
authors.initials: PJ
authors.lastname: Flynn
authors.forename: Alvaro
authors.initials: A
authors.lastname: Moreno-Aspitia
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
authors.forename: Betsy
authors.initials: B
authors.lastname: LaPlant
authors.forename: Mark B
authors.initials: MB
authors.lastname: Juckett
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D012307:Risk Factors; D016879:Salvage Therapy; D015996:Survival Rate; D007211:Indoles
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; C500926:cediranib; D007211:Indoles
keywords: Myeloid leukemias and dysplasias; pharmacotherapeutics; signal transduction