rdf:type |
|
lifeskim:mentions |
umls-concept:C0001792,
umls-concept:C0010711,
umls-concept:C0011015,
umls-concept:C0011900,
umls-concept:C0023467,
umls-concept:C0030705,
umls-concept:C0080103,
umls-concept:C0087111,
umls-concept:C0139121,
umls-concept:C0332287,
umls-concept:C0376622,
umls-concept:C0449438,
umls-concept:C0450442,
umls-concept:C1522609,
umls-concept:C1554112,
umls-concept:C1704939,
umls-concept:C1823242
|
pubmed:issue |
8
|
pubmed:dateCreated |
2005-10-5
|
pubmed:abstractText |
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.
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
AIM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Oct
|
pubmed:issn |
0006-4971
|
pubmed:author |
pubmed-author:BurnettAlan KAK,
pubmed-author:CrumpMichaelM,
pubmed-author:DuganMargaretM,
pubmed-author:FerrantAugustinA,
pubmed-author:FeyMartin FMF,
pubmed-author:KnaufWolfgang UWU,
pubmed-author:LöwenbergBobB,
pubmed-author:OssenkoppeleGert JGJ,
pubmed-author:PiccalugaPier PaoloPP,
pubmed-author:SelleslagDominikD,
pubmed-author:ShepherdJohnJ,
pubmed-author:SonneveldPieterP,
pubmed-author:TheobaldMatthiasM,
pubmed-author:VellengaEdoE,
pubmed-author:VerhoefGregor E GGE,
pubmed-author:van der HoltBronnoB
|
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
106
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
2646-54
|
pubmed:dateRevised |
2007-11-15
|
pubmed:meshHeading |
pubmed-meshheading:15994288-Aged,
pubmed-meshheading:15994288-Aged, 80 and over,
pubmed-meshheading:15994288-Cyclosporins,
pubmed-meshheading:15994288-Cytarabine,
pubmed-meshheading:15994288-Daunorubicin,
pubmed-meshheading:15994288-Drug Therapy, Combination,
pubmed-meshheading:15994288-Female,
pubmed-meshheading:15994288-Follow-Up Studies,
pubmed-meshheading:15994288-Humans,
pubmed-meshheading:15994288-Leukemia, Myeloid, Acute,
pubmed-meshheading:15994288-Male,
pubmed-meshheading:15994288-Middle Aged,
pubmed-meshheading:15994288-P-Glycoprotein,
pubmed-meshheading:15994288-Survival Rate,
pubmed-meshheading:15994288-Treatment Outcome
|
pubmed:year |
2005
|
pubmed:articleTitle |
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.
|
pubmed:affiliation |
Department of Hematology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands. p.sonneveld@erasmusmc.nl.
|
pubmed:publicationType |
Journal Article,
Clinical Trial,
Randomized Controlled Trial,
Research Support, Non-U.S. Gov't
|