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Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein: results of a randomized study.

Author(s): Wattel E, Solary E, Hecquet B, Caillot D, Ifrah N, Brion A, Mahe B, Milpied N, Janvier M, Guerci A, Rochant H, Cordonnier C, Dreyfus F, Buzyn A, Hoang-Ngoc L, Stoppa AM, Gratecos N, Sadoun A, Stamatoulas A, Tilly H, Brice P, Maloisel F, Lioure B, Desablens B, Fenaux P

Affiliation(s): Groupe Francais des Myelodysplasies, Service des Maladies du Sang, CHU, Lille, France.

Publication date & source: 1998-09, Br J Haematol., 102(4):1015-24.

Publication type: Clinical Trial; Randomized Controlled Trial

Intensive chemotherapy produces a lower complete remission (CR) rate in the myelodysplastic syndromes (MDS) than in de novo acute myeloid leukaemia (AML), possibly due in part to a higher incidence of P glycoprotein (PGP) expression in MDS blast cells. We designed a randomized trial of intensive chemotherapy with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged < or = 65 years with high-risk MDS. Patients were randomized to receive mitoxantrone 12 mg/m2/d days 2-5 + AraC 1 g/m2/12 h days 1-5, with (Q+) or without (Q-) quinine (30 mg/kg/d). 131 patients were included. PGP expression analysis was successful in 91 patients. In the 42 PGP-positive cases, 13/25 (52%) patients in the Q+ group achieved CR, compared to 3/17 (18%) patients in the Q- group (P = 0.02) and median Kaplan-Meier survival was 13 months in the Q+ group, and 8 months in the Q- group (P = 0.01). No life-threatening toxicity was observed with quinine. In conclusion, the results of this randomized study show that quinine increases the CR rate and survival in PGP-positive MDS cases treated with intensive chemotherapy.

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