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Dasatinib in combination with fludaralaine in patients with refractory chronic lymphocytic leukemia: A multicenter phase 2 study

Kater, 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 journalArticleAcademicpeer-review

  • Arnon P. Kater
  • Marjolein Spiering
  • Roberto D. Liu
  • G. Doreen te Raa
  • E. Slinger
  • Sanne H. Tonino
  • Marielle M. Beckers
  • Simon Daenen
  • Jeanette K. Doorduijn
  • Nienke A. G. Lankheet
  • Dieuwertje M. Luijks
  • Eric Eldering
  • Marnius H. J. van Oers

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.

Original languageEnglish
Pages (from-to)34-41
Number of pages8
JournalLeukemia Research
Volume38
Issue number1
Publication statusPublished - Jan-2014

    Keywords

  • 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

ID: 16066568