title: An open-label, Phase I study of cediranib (RECENTIN) in patients with acute myeloid leukemia.
abstract: VEGFR and c-Kit signaling pathways may contribute to the pathophysiology of acute myeloid leukemia (AML). Thirty-five patients with AML received cediranib (RECENTIN), an oral, highly potent VEGF signaling inhibitor with c-Kit activity, at doses of < or =30 mg/day. The most common adverse events were diarrhea, hypertension and fatigue. Six patients experienced an objective response (3 each at 20 and 30 mg). Dose- and time-dependent reductions in sVEGFR-2 were observed, and there was a positive correlation between cediranib exposure and the change in plasma VEGF levels from baseline. Cediranib was generally well tolerated and showed preliminary evidence of activity as a monotherapy.
authors.affiliation: Department of Oncology, Hematology, BMT with section Pneumology Hubertus Wald Tumorzentrum - University Cancer Center Hamburg University Medical Center Hamburg Eppendorf 20246 Hamburg, Germany. Fiedler@uke.uni-hamburg.de
authors.forename: Walter
authors.initials: W
authors.lastname: Fiedler
authors.forename: Rolf
authors.initials: R
authors.lastname: Mesters
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Ute
authors.initials: U
authors.lastname: Zirrgiebel
authors.forename: Jane D
authors.initials: JD
authors.lastname: Robertson
authors.forename: Tom A
authors.initials: TA
authors.lastname: Puchalski
authors.forename: Barbara
authors.initials: B
authors.lastname: Collins
authors.forename: Juliane M
authors.initials: JM
authors.lastname: Jürgensmeier
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003967:Diarrhea / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects; D007211:Indoles
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D011799:Quinazolines; D040301:Vascular Endothelial Growth Factor Receptor-2; C500926:cediranib; D007211:Indoles