Addition of cyclosporin A to the combination of mitoxantrone and etoposide to overcome resistance to chemotherapy in refractory or relapsing acute myeloid leukaemia: A randomised phase II trial from HOVON, the Dutch–Belgian Haemato-Oncology Working Group for adults

S.M.G.J. Daenen, B. van der Holt, G.E.G. Verhoef, B. Lowenberg, P.W. Wijermans, P.C. Huijgens, R.V.M. Kooy, H.C. Schouten, M.H.H. Kramer, A. Ferrant, E. van den Berg, M.M.C. Steijaert, L.F. Verdonck, P. Sonneveld

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    Abstract

    Cyclosporin A (CsA) inhibits the P-gp pump that can be responsible for failure of cytostatic treatment in acute myeloid leukaemia (AML). Eighty patients with relapsing/refractory AML were randomly assigned to mitoxantrone (M) and etoposide (VP) (MVP) in unmitigated antileukaemic doses with or without CsA, to investigate if toxicity was manageable and if antileukaemic therapy could be improved. CsA did not delay haematological recovery, but fewer CsA patients received post-induction therapy because of haematological and non-haematological toxicity. CR rate was 43% for MVP and 53% for CsA; DFS was 9 and 8 months, and OS 8 and 9 months, respectively. Seventeen of 38 CR patients proceeded to stem cell transplantation (SCT). After a median follow-up of 66 months, six patients were still alive. Addition of CsA did not improve treatment outcome, possibly due to inadequate post-induction therapy as a result of increased toxicity.
    Original languageEnglish
    Pages (from-to)1057-1067
    Number of pages11
    JournalLeukemia Research
    Volume28
    Issue number10
    DOIs
    Publication statusPublished - Oct-2004

    Keywords

    • acute myeloid leukaemia
    • resistance
    • cyclosporin A
    • efflux pump
    • P-glycoprotein
    • MULTIDRUG-RESISTANCE
    • P-GLYCOPROTEIN
    • DRUG-RESISTANCE
    • HUMAN CANCER
    • BLAST CELLS
    • PERIPHERAL-BLOOD
    • ONCOLOGY-GROUP
    • MDR1 GENE
    • EXPRESSION
    • PROTEIN

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