An open-label, Phase I study of cediranib (RECENTIN) in patients with acute myeloid leukemia.
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.
Fiedler
Walter
W
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
Mesters
Rolf
R
Heuser
Michael
M
Ehninger
Gerhard
G
Berdel
Wolfgang E
WE
Zirrgiebel
Ute
U
Robertson
Jane D
JD
Puchalski
Tom A
TA
Collins
Barbara
B
Jürgensmeier
Juliane M
JM
Serve
Hubert
H
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
D019009:Proto-Oncogene Proteins c-kit; D011799:Quinazolines; D040301:Vascular Endothelial Growth Factor Receptor-2; C500926:cediranib; D007211:Indoles