Clofarabine doubles the response rate in older patients with acute myeloid
leukemia but does not improve survival.
Author(s): Burnett AK(1), Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J,
McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML
Working Group.
Affiliation(s): Author information:
(1)Department of Haematology, Cardiff University School of Medicine, Cardiff, United
Kingdom. burnettak@cardiff.ac.uk.
Publication date & source: 2013, Blood. , 122(8):1384-94
Better treatment is required for older patients with acute myeloid leukemia (AML)
not considered fit for intensive chemotherapy. We report a randomized comparison
of low-dose Ara-C (LDAC) vs the novel nucleoside, clofarabine, in untreated older
patients with AML and high-risk myelodysplastic syndrome (MDS). A total of 406
patients with de novo (62%), secondary disease (24%), or high-risk MDS (>10%
marrow blasts) (15%), median age 74 years, were randomized to LDAC 20 mg twice
daily for 10 days every 6 weeks or clofarabine 20 mg/m(2) on days 1 to 5, both
for up to 4 courses. These patients had more adverse demographics than
contemporaneous intensively treated patients. The overall remission rate was 28%,
and 2-year survival was 13%. Clofarabine significantly improved complete
remission (22% vs 12%; hazard ratio [HR] = 0.47 [0.28-0.79]; P = .005) and
overall response (38% vs 19%; HR = 0.41 [0.26-0.62]; P < .0001), but there was no
difference in overall survival, explained by poorer survival in the clofarabine
patients who did not gain complete remission and also following relapse.
Clofarabine was more myelosuppressive and required more supportive care. Although
clofarabine doubled remission rates, overall survival was not improved overall or
in any subgroup. The treatment of patients of the type treated here remains a
major unmet need.
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