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Prepublished online as a Blood First Edition Paper on March 27, 2003; DOI 10.1182/blood-2002-11-3419. This Article Full Text (PDF) All Versions of this Article: 2002-11-3419v1 102/4/1202    most recent Alert me when this article is cited Alert me if a correction is posted 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 Solary, E. Articles by Harousseau, J.-L. Search for Related Content PubMed PubMed Citation Articles by Solary, E. Articles by Harousseau, J.-L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted November 15, 2002 Accepted March 20, 2003 Quinine as a multidrug resistance inhibitor: a phase III multicentric randomized study in adult de novo acute myelogenous leukemia Eric Solary, Bernard Drenou, Lydia Campos, Patricia de Cremoux, Francine Mugneret, Philippe Moreau, Bruno Lioure, Annie Falkenrodt, Brigitte Witz, Marc Bernard, Mathilde Hunault-Berger, Martine Delain, Jose Fernandes, Christiane Mounier, Francois Guilhot, Francine Garnache, Christian Berthou, Fawzi Kara-Slimane, and Jean-Luc Harousseau* Hematology Department, CHU, Dijon, France Hematology Department, CHU, Rennes, France Hematology Department, CHU, Saint-Etienne, France Transfer Biology Department, Institut Curie, Paris, France Cytogenetic Laboratory, CHU, Dijon, France Hematology Department, CHU, Nantes, France Hematology Department, CHU, Strasbourg, France Hematology Department, CHU, Nancy, France Hematology Department, CHU, Angers, France Hematology Department, CHU, Tours, France Hematology Department, CHU, Amiens, France Hematology Department, CHU, Poitiers, France Hematology Department, CHU, Besancon, France Hematology Department, CHU, Brest, France * Corresponding author; email: jlharousseau{at}sante.univ-nantes.fr. Based on our previous demonstration that quinine could be used clinically to reverse P-glycoprotein-mediated resistance, we designed a multicenter, randomized trial aiming to determine whether quinine would improve the survival of adult patients (15-60 years old) with de novo acute myelogenous leukemia (AML). These patients randomly received (n=213) or not (n = 212) a 30 mg/kg/d continuous iv infusion of quinine in combination with induction chemotherapy combining idarubicine and cytarabine and, depending on bone marrow examination at day 20, an additional course of cytarabine and mitoxantrone. The mean steady-state quinine concentration was 7.8 mg/L and the mean MDR reversing activity of serum was 1.96. Complete remission (CR) was obtained in 344 patients (80.9%) without significant influence of quinine. Eighty-two patients in CR were assigned to HLA-matched bone-marrow transplantation whereas 262 were assigned to two courses of intensive consolidation chemotherapy, with or without quinine depending on initial randomization. The 4-year actuarial overall survival (OS) of the 425 eligible patients was 42.0 +/- 2.5 %, without significant influence of quinine. Out of 160 patients that could be studied, 54 demonstrated rhodamine 123 efflux. In these patients, quinine significantly improved the CR rate from 12/25 (48.0%) to 24/29 (82.8%) (P = 0.01). However, there was no significant difference in OS. Neither mdr1 gene nor P-glycoprotein expression influenced the outcome. We conclude that quinine does not improve the survival of adult patients with de novo AML, even though it improves CR rate in a small subgroup of patients defined by rhodamine 123 efflux. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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