The anti-angiogenesis agent, AG-013736, has minimal activity in elderly patients with poor prognosis acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
AG-013736 is an oral anti-angiogenesis agent with activity against a variety of receptor tyrosine kinases, including VEGFR-1, VEGFR-2, VEGFR-3, c-kit, and PDGFR-beta. A phase 2 study was conducted in patients with poor prognosis AML or MDS. Twelve patients (six AML; six MDS) were treated with AG-013736 at a dose of 10mg orally daily for a median of 56 days (range, 1-248 days). Median age was 80 years (range, 58-88 years). Grade 3 or 4 drug-related toxicities included hypertension (42%), mucositis (8%) and deep venous thrombosis (8%). No objective responses occurred; two patients with MDS had stable disease for 8.3 and 6.2 months, respectively. Bone marrow expression of VEGFR-1 and VEGFR-2 was observed in 11% and 0% of patients, respectively. Sustained decreases in soluble VEGFR-2 plasma levels with concomitant elevation in plasma VEGF and placental growth factor levels were obtained during the course of therapy with AG-013736. AG-01736 had minimal biologic or clinical activity in this elderly patient population.
Giles
Francis J
FJ
Department of Leukemia, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030, USA. frankgiles@aol.com
Bellamy
William T
WT
Estrov
Zeev
Z
O'Brien
Susan M
SM
Verstovsek
Srdan
S
Ravandi
Farhad
F
Beran
Miloslav
M
Bycott
Paul
P
Pithavala
Yazdi
Y
Steinfeldt
Heidi
H
Reich
Steven D
SD
List
Alan F
AF
Yee
Karen W L
KW
D000208:Acute Disease; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077784:Axitinib; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D007191:Indazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy*; D000072483:Placenta Growth Factor; D011237:Predictive Value of Tests; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors / Q000097:blood; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000097:blood / Q000187:drug effects; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000097:blood
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D000077784:Axitinib; D019009:Proto-Oncogene Proteins c-kit; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2