Addition of cyclosporin A to the combination of mitoxantrone and etoposide to overcome resistance to chemotherapy in refractory or relapsing acute myeloid leukaemia:

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.

Abbreviations:  ABC, ATP-binding cassette, AML, acute myeloid leukaemia, BCRP, breast cancer resistance protein, BM, bone marrow, CI, confidence intervals, CR, complete remission, CsA, cyclosporin A, CTC, common toxicity criteria, DFS, disease-free survival, EFS, event-free survival, EMIT, enzyme multiplied immuno-assay technique, LRP, lung resistance-related protein, MDR, multidrug resistance, MRP, multidrug resistance-related protein, MVP, mitoxantrone / vepesid, NR, non-response, PR, partial response, OS, overall survival, PB, peripheral blood, P-gp, P-glycoprotein, SCT, stem cell transplantation, WBC, white blood cell count

Keywords:  Acute myeloid leukaemia, Resistance, Cyclosporin A, Efflux pump, P-glycoprotein