TY - JOUR
T1 - A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome
AU - Faderl, Stefan
AU - Garcia-Manero, Guillermo
AU - Jabbour, Elias
AU - Ravandi, Farhad
AU - Borthakur, Gautam
AU - Estrov, Zeev
AU - Gandhi, Varsha
AU - Byrd, Anna L.
AU - Kwari, Monica
AU - Cortes, Jorge
AU - Kantarjian, Hagop M.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/2/1
Y1 - 2012/2/1
N2 - BACKGROUND: Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited. METHODS: The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m 2 vs 30 mg/m 2 daily à - 5 days) of intravenous clofarabine in patients with higher-risk MDS. Fifty-eight patients with a median age of 68 years (range, 25-89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts. RESULTS: The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m 2 and 29% at 30 mg/m 2). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8-week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m 2 of clofarabine. Myelosuppression and infectious complications were frequent. CONCLUSIONS: Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued.
AB - BACKGROUND: Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited. METHODS: The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m 2 vs 30 mg/m 2 daily à - 5 days) of intravenous clofarabine in patients with higher-risk MDS. Fifty-eight patients with a median age of 68 years (range, 25-89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts. RESULTS: The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m 2 and 29% at 30 mg/m 2). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8-week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m 2 of clofarabine. Myelosuppression and infectious complications were frequent. CONCLUSIONS: Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued.
KW - DNA methyltransferase inhibitors
KW - clofarabine
KW - myelodysplastic syndrome
KW - nucleoside analogs
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U2 - 10.1002/cncr.26327
DO - 10.1002/cncr.26327
M3 - Article
C2 - 21751197
AN - SCOPUS:84856232797
SN - 0008-543X
VL - 118
SP - 722
EP - 728
JO - Cancer
JF - Cancer
IS - 3
ER -