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
Leukemia Research: clinical and laboratory studies , Volume 28 - Issue 10 p. 1057- 1067
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.
|ABC, acute myeloid leukaemia, AML, ATP-binding cassette, BCRP, BM, bone marrow, breast cancer resistance protein, CI, common toxicity criteria, complete remission, confidence intervals, CR, CsA, CTC, cyclosporin A, DFS, disease-free survival, EFS, event-free survival|
|Leukemia Research: clinical and laboratory studies|
|Organisation||Department of Hematology|
Daenen, S.M.G.J, van der Holt, B, Verhoef, G.E.G, Löwenberg, B, Wijermans, P.W, Huijgens, P.C, … Sonneveld, P. (2004). 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. Leukemia Research: clinical and laboratory studies, 28(10), 1057–1067. doi:10.1016/j.leukres.2004.03.001