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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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-β. 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 10 mg 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.

Original languageEnglish (US)
Pages (from-to)801-811
Number of pages11
JournalLeukemia Research
Volume30
Issue number7
DOIs
StatePublished - Jul 1 2006

Keywords

  • AG-013736
  • AML
  • Angiogenesis inhibitor
  • Microvessel density
  • Myelodysplasia
  • Soluble VEGFR-2

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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