Dasatinib in combination with fludaralaine in patients with refractory chronic lymphocytic leukemia: A multicenter phase 2 studyKater, A. P., Spiering, M., Liu, R. D., te Raa, G. D., Slinger, E., Tonino, S. H., Beckers, M. M., Daenen, S., Doorduijn, J. K., Lankheet, N. A. G., Luijks, D. M., Eldering, E. & van Oers, M. H. J., Jan-2014, In : Leukemia Research. 38, 1, p. 34-41 8 p.
Research output: Contribution to journal › Article › Academic › peer-review
Resistance to chemotherapy-induced apoptosis in CLL is associated with overexpression of antiapoptotic proteins induced by signals from the microenvironment. In vitro, dasatinib effectively inhibits expression of anti-apoptotic regulators and restores fludarabine sensitivity in activated CLL.
The aim of this study was to evaluate efficacy of one cycle of dasatinib monotherapy (100 mg/day, days 1-28) followed by combination of dasatinib with fludarabine (40 mg/m(2)/day, days 1-3 every 28 day) for a total of it cycles in fludarabine-refractory. The primary endpoint was overall response rate according to the IWCLL'08 criteria.
20 patients were enrolled: 18 completed at least one cycle of treatment of which 67% finishsed at Pact 2 cycles of combination treatment. 3 of these 18 patients reached a format PR (16,7%). Majority of patients obtained some reduction in lymph node (LN) size. Most frequent toxicity was related to myelosuppression.
NF-kappa B RNA expression levels of circulating CLL cells decreased whereas the levels of pro-apoptotic NOXA increased during trot merit.
In conclusion, dasatinib/fludarabine combination has modest clinical efficacy in fludarabine-refractory patients. (C) 2013 Elsevier Ltd, All rights reserved.
|Number of pages||8|
|Publication status||Published - Jan-2014|
- CLL, Hudarabine refractory, Microenvironment, Kinase inhibitor, Dasatinib, NOXA, KINASE INHIBITOR DASATINIB, B-CELL RECEPTOR, IN-VITRO, NOXA/MCL-1 BALANCE, RESPONSE CRITERIA, TYROSINE KINASE, SALVAGE THERAPY, SINGLE-AGENT, FLUDARABINE, ALEMTUZUMAB