Antiangiogenic activity of thalidomide in combination with fludarabine, carboplatin, and topotecan for high-risk acute myelogenous leukemia.
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.
Barr
Paul
P
Department of Hematology and Oncology, University Hospitals Case Medical Center, Cleveland 44106, USA.
Fu
Pingfu
P
Lazarus
Hillard
H
Kane
Donna
D
Meyerson
Howard
H
Hartman
Paul
P
Reyes
Rania
R
Creger
Richard
R
Stear
Karen
K
Laughlin
Mary
M
Tse
William
W
Cooper
Brenda
B
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*
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D019772:Topotecan; D016190:Carboplatin; D014740:Vidarabine; C024352:fludarabine