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: Francis J Giles, William T Bellamy, Zeev Estrov, Susan M O'Brien, Srdan Verstovsek, Farhad Ravandi, Miloslav Beran, Paul Bycott, Yazdi Pithavala, Heidi Steinfeldt, Steven D Reich, Alan F List, Karen W L Yee
• Journal: Leukemia research (Leuk Res) Vol. 30 Issue 7 Pg. 801-11 (Jul 2006) ISSN: 0145-2126 [Print] England
• PMID: 16332390 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Imidazoles
• Indazoles
• PGF protein, human
• Pregnancy Proteins
• Placenta Growth Factor
• Axitinib
• Proto-Oncogene Proteins c-kit
• Vascular Endothelial Growth Factor Receptor-1
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Acute Disease
• Administration, Oral
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors (administration & dosage, adverse effects, pharmacokinetics)
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Axitinib
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Humans
• Imidazoles (administration & dosage, adverse effects, pharmacokinetics)
• Immunohistochemistry
• Indazoles (administration & dosage, adverse effects, pharmacokinetics)
• Leukemia, Myeloid (diagnosis, drug therapy)
• Male
• Middle Aged
• Myelodysplastic Syndromes (diagnosis, drug therapy)
• Placenta Growth Factor
• Predictive Value of Tests
• Pregnancy Proteins (antagonists & inhibitors, blood)
• Prognosis
• Proto-Oncogene Proteins c-kit (blood, drug effects)
• Treatment Outcome
• Vascular Endothelial Growth Factor Receptor-1 (antagonists & inhibitors, blood)
• Vascular Endothelial Growth Factor Receptor-2 (antagonists & inhibitors, blood)