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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2646-2654. Prepublished online as a Blood First Edition Paper on June 30, 2005; DOI 10.1182/blood-2005-04-1395. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1395v1 106/8/2646    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by van der Holt, B. Articles by Sonneveld, P. Search for Related Content PubMed PubMed Citation Articles by van der Holt, B. Articles by Sonneveld, P. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS 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 Bronno van der Holt, Bob Löwenberg, Alan K. Burnett, Wolfgang U. Knauf, John Shepherd, Pier Paolo Piccaluga, Gert J. Ossenkoppele, Gregor E. G. Verhoef, Augustin Ferrant, Michael Crump, Dominik Selleslag, Matthias Theobald, Martin F. Fey, Edo Vellenga, Margaret Dugan, Pieter Sonneveld, on behalf of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) and the United Kingdom Medical Research Council (MRC) From the Department of Trials & Statistics–HOVON Data Center, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam, The Netherlands; Department of Hematology, Erasmus MC, Rotterdam, The Netherlands; Department of Hematology, Wales School of Medicine, Cardiff University, United Kingdom; Department of Hematology, University Hospital Benjamin Franklin, Berlin, Germany; Department of Medicine, Division of Hematology, Vancouver Hospital, Canada; Department of Hematology and Medical Oncology "L. and A. Seràgnoli," S. Orsola-Malpighi Hospital, University of Bologna, Italy; Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands; Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium; Department of Hematology, Cliniques Universitaires St Luc, Brussels, Belgium; Division of Hematology and Medical Oncology, Princess Margaret Hospital, Toronto, Canada; Department of Hematology, St Jan's Hospital, Brugge, Belgium; Department of Hematology and Oncology, Johannes Gutenberg University, Mainz, Germany; Department of Medical Oncology, Inselspital Bern, Switzerland; Department of Internal Medicine, University Medical Center Groningen, The Netherlands; and Early Clinical Development Oncology, Novartis Pharmaceuticals, East Hanover, NJ. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Estey Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Patients J. Clin. Oncol., May 10, 2007; 25(14): 1908 - 1915. [Abstract] [Full Text] [PDF] H. P. Erba Prognostic Factors in Elderly Patients with AML and the Implications for Treatment Hematology, January 1, 2007; 2007(1): 420 - 428. [Abstract] [Full Text] [PDF] C. M. Zwaan, M. L. den Boer, K. M. Kazemier, K. Hahlen, A. H. Loonen, D. Reinhardt, U. Creutzig, G. J. L. Kaspers, R. Pieters, G. V. Dahl, et al. Does modulation of P-glycoprotein have clinical relevance in pediatric acute myeloid leukemia? Blood, June 15, 2006; 107(12): 4975 - 4977. [Full Text] [PDF] B. I. Sikic Multidrug resistance and stem cells in acute myeloid leukemia. Clin. Cancer Res., June 1, 2006; 12(11): 3231 - 3232. [Full Text] [PDF] M. H.G.P. Raaijmakers, E. P.L.M. de Grouw, B. A. van der Reijden, T. J.M. de Witte, J. H. Jansen, and R. A.P. Raymakers ABCB1 Modulation Does Not Circumvent Drug Extrusion from Primitive Leukemic Progenitor Cells and May Preferentially Target Residual Normal Cells in Acute Myelogenous Leukemia. Clin. Cancer Res., June 1, 2006; 12(11): 3452 - 3458. [Abstract] [Full Text] [PDF]

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