The anti-angiogenesis agent, AG-013736, has minimal activity in elderly patients with poor prognosis acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

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

doi:10.1016/j.leukres.2005.10.024

The anti-angiogenesis agent, AG-013736, has minimal activity in elderly patients with poor prognosis acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

Leuk Res. 2006 Jul;30(7):801-11. doi: 10.1016/j.leukres.2005.10.024. Epub 2005 Dec 5.

Authors

Francis J Giles¹, 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

Affiliation

¹ Department of Leukemia, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030, USA. [email protected]

PMID: 16332390
DOI: 10.1016/j.leukres.2005.10.024

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.

Publication types

Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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