A randomized trial of liposomal daunorubicin and cytarabine versus liposomal daunorubicin and topotecan with or without thalidomide as initial therapy for patients with poor prognosis acute myelogenous leukemia or myelodysplastic syndrome.
BACKGROUND
Because angiogenesis may play a role in the pathogenesis of acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), and thalidomide (Th) has shown significant anti-angiogenic activity, this study was designed to investigate the potential role of Th in the treatment of patients with AML and MDS and the possible role of a non-ara-C-containing regimen.


METHODS
Adults with AML or high-risk MDS and cytogenetic abnormalities other than inv (16), t(8;21), -Y or -X were randomized to receive liposomal daunorubicin (DNX) and ara-C (DA) or DNX and topotecan (DT). Within each arm, patients were randomized to receive chemotherapy alone (DA or DT) or with thalidomide (DATh or DTTh). Vascular endothelial growth factor (VEGF) plasma levels and microvascular density was measured before and after therapy. Eighty-four patients (median age, 65 years; range, 27-84 years) were treated.


RESULTS
None of 11 patients treated with DT or DTTh responded and these arms were closed. Seventeen of 37 patients treated with DA and 15 of 36 treated with DATh achieved an early complete remission. Median complete response duration was 38 and 34 weeks (P = 0.57) and median survival 35 and 28 weeks (P = 0.15), respectively. Patients with high pretreatment VEGF levels had an inferior survival. There was no significant difference in the changes in VEGF levels or microvascular density after treatment in patients who did versus those who did not receive thalidomide.


CONCLUSIONS
The authors concluded that thalidomide in combination with chemotherapy does not result in clinical benefit in patients with AML or high-risk MDS.
Cortes
Jorge
J
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. jcortes@mdanderson.org
Kantarjian
Hagop
H
Albitar
Maher
M
Thomas
Deborah
D
Faderl
Stefan
S
Koller
Charles
C
Garcia-Manero
Guillermo
G
Giles
Francis
F
Andreeff
Michael
M
O'Brien
Susan
S
Keating
Michael
M
Estey
Elihu
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D016228:Endothelial Growth Factors / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008081:Liposomes; D008222:Lymphokines / Q000097:blood; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003561:Cytarabine; D013792:Thalidomide; D019772:Topotecan; D003630:Daunorubicin