title: The anti-angiogenesis agent, AG-013736, has minimal activity in elderly patients with poor prognosis acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
abstract: 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.
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030, USA. frankgiles@aol.com
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: William T
authors.initials: WT
authors.lastname: Bellamy
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Miloslav
authors.initials: M
authors.lastname: Beran
authors.forename: Paul
authors.initials: P
authors.lastname: Bycott
authors.forename: Yazdi
authors.initials: Y
authors.lastname: Pithavala
authors.forename: Heidi
authors.initials: H
authors.lastname: Steinfeldt
authors.forename: Steven D
authors.initials: SD
authors.lastname: Reich
authors.forename: Alan F
authors.initials: AF
authors.lastname: List
authors.forename: Karen W L
authors.initials: KW
authors.lastname: Yee
mesh_terms: 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
chemical_list: 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