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.
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.
Department of Haematology, University Hospital, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. s.m.g.daenen@int.azg.nl
Simon
S
Daenen
Bronno
B
van der Holt
Gregor E G
GE
Verhoef
Bob
B
Löwenberg
Pierre W
PW
Wijermans
Peter C
PC
Huijgens
Rien
R
van Marwijk Kooy
Harry C
HC
Schouten
Mark H H
MH
Kramer
Augustin
A
Ferrant
Eva
E
van den Berg
Monique M C
MM
Steijaert
Leo F
LF
Verdonck
Pieter
P
Sonneveld
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D012008:Recurrence; D012044:Regression Analysis; D016019:Survival Analysis; D016896:Treatment Outcome
D005047:Etoposide; D016572:Cyclosporine; D008942:Mitoxantrone