The first 2 authors contributed equally to this work.
Results of a multicenter phase II trial for older patients with c-Kit-positive acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS) using low-dose Ara-C and Imatinib
Article first published online: 6 FEB 2007
Copyright © 2007 American Cancer Society
Volume 109, Issue 5, pages 907–914, 1 March 2007
How to Cite
Heidel, F., Cortes, J., Rücker, F. G., Aulitzky, W., Letvak, L., Kindler, T., Huber, C., Döhner, H., Kantarjian, H. and Fischer, T. (2007), Results of a multicenter phase II trial for older patients with c-Kit-positive acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS) using low-dose Ara-C and Imatinib. Cancer, 109: 907–914. doi: 10.1002/cncr.22471
- Issue published online: 22 FEB 2007
- Article first published online: 6 FEB 2007
- Manuscript Accepted: 20 NOV 2006
- Manuscript Revised: 13 NOV 2006
- Manuscript Received: 21 SEP 2006
- low-dose Ara-C;
Imatinib (IM) is a potent tyrosine kinase inhibitor of c-Kit. c-Kit is expressed in the majority of patients with acute myeloid leukemia (AML). Whereas clinical trials evaluating monotherapy with IM in AML revealed low response rates, Ara-C and IM showed synergistic effects in vitro. This suggested evaluation of a combination treatment.
Low-dose Ara-C (LDAC) combined with IM was tested to determine the efficacy and safety of this regimen. Forty patients from 4 centers with c-Kit-positive AML (n = 34) and high-risk myelodysplastic syndrome (HR-MDS) (n = 6) with a median age of 73 years were enrolled. They were either not eligible for myelosuppressive therapy and/or had recurring/refractory disease.
Thirty-eight patients were evaluable for analysis. In 6 of 38 patients a blast response was observed. Eight of 38 patients showed stable disease for more than 2 months. The objective hematologic response rate was low (11%), with 2 patients showing hematologic improvement and 1 each with a partial response (PR) or complete response (CR). Median overall survival was 138 days, with 20% of patients alive after an observation period of 600 days. Study medication was applied in an ambulatory setting with minimal hospitalization time, an early mortality rate of only 18.9%, and a low toxicity rate.
LDAC plus IM does not appear to be inferior in older AML patients incomparison with historic controls receiving myelosuppressive therapy. However, this trial also shows that LDAC/IM does not appear to be more effective than LDAC monotherapy in a patient population not selected for appropriate molecular markers. Cancer 2007 © 2007 American Cancer Society.