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Title: The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis
Authors: van der Holt, Bronno ×
Löwenberg, Bob
Burnett, Alan K
Knauf, Wolfgang U
Shepherd, John
Piccaluga, Pier Paolo
Ossenkoppele, Gert J
Verhoef, Gregor
Ferrant, Augustin
Crump, Michael
Selleslag, Dominik
Theobald, Matthias
Fey, Martin F
Vellenga, Edo
Dugan, Margaret
Sonneveld, Pieter #
Issue Date: Oct-2005
Series Title: Blood vol:106 issue:8 pages:2646-54
Abstract: To determine whether MDR1 reversal by the addition of the P-glycoprotein (P-gp) inhibitor PSC-833 to standard induction chemotherapy would improve event-free survival (EFS), 419 untreated patients with acute myeloid leukemia (AML) aged 60 years and older were randomized to receive 2 induction cycles of daunorubicin and cytarabine with or without PSC-833. Patients in complete remission were then given 1 consolidation cycle without PSC-833. Neither complete response (CR) rate (54% versus 48%; P = .22), 5-year EFS (7% versus 8%; P = .53), disease-free survival (DFS; 13% versus 17%; P = .06) nor overall survival (OS; 10% in both arms; P = .52) were significantly improved in the PSC-833 arm. An integrated P-gp score (IPS) was determined based on P-gp function and P-gp expression in AML cells obtained prior to treatment. A higher IPS was associated with a significantly lower CR rate and worse EFS and OS. There was no significant interaction between IPS and treatment arm with respect to CR rate and survival, indicating also a lack of benefit of PSC-833 in P-gp-positive patients. The role of strategies aimed at inhibitory P-gp and other drug-resistance mechanisms continues to be defined in the treatment of patients with AML.
URI: 
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hematology Section (-)
× corresponding author
# (joint) last author

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