title: Antiangiogenic activity of thalidomide in combination with fludarabine, carboplatin, and topotecan for high-risk acute myelogenous leukemia.
abstract: Forty-two patients with poor prognosis AML were enrolled in a phase II study combining fludarabine, carboplatin, and topotecan (FCT) with thalidomide. Laboratory correlates included serum vascular endothelial growth factor levels (VEGF) and bone marrow microvascular density (MVD). Ten of 42 (24%) patients achieved a complete remission (CR or CRp). Serious thrombotic adverse events were observed in 5 patients suggesting that the combination of cytotoxic chemotherapy and thalidomide may be thrombogenic despite significant thrombocytopenia. VEGF did not correlate with response to therapy, while a trend towards decreased MVD was noted in patients who achieved CR. The addition of thalidomide did not significantly influence angiogenic markers. It is not clear that thalidomide adds any efficacy to the FCT regimen.
authors.affiliation: Department of Hematology and Oncology, University Hospitals Case Medical Center, Cleveland 44106, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Barr
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: Hillard
authors.initials: H
authors.lastname: Lazarus
authors.forename: Donna
authors.initials: D
authors.lastname: Kane
authors.forename: Howard
authors.initials: H
authors.lastname: Meyerson
authors.forename: Paul
authors.initials: P
authors.lastname: Hartman
authors.forename: Rania
authors.initials: R
authors.lastname: Reyes
authors.forename: Richard
authors.initials: R
authors.lastname: Creger
authors.forename: Karen
authors.initials: K
authors.lastname: Stear
authors.forename: Mary
authors.initials: M
authors.lastname: Laughlin
authors.forename: William
authors.initials: W
authors.lastname: Tse
authors.forename: Brenda
authors.initials: B
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D013792:Thalidomide / Q000008:administration & dosage*; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D019772:Topotecan; D016190:Carboplatin; D014740:Vidarabine; C024352:fludarabine