TY - JOUR
T1 - Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein
T2 - Results of a randomized study
AU - Wattel, E.
AU - Solary, E.
AU - Hecquet, B.
AU - Caillot, D.
AU - Ifrah, N.
AU - Brion, A.
AU - Mahé, B.
AU - Milpied, N.
AU - Janvier, M.
AU - Guerci, A.
AU - Rochant, H.
AU - Cordonnier, C.
AU - Dreyfus, F.
AU - Buzyn, A.
AU - Hoang-Ngoc, L.
AU - Stoppa, A. M.
AU - Gratecos, N.
AU - Sadoun, A.
AU - Stamatoulas, A.
AU - Tilly, H.
AU - Brice, P.
AU - Maloisel, F.
AU - Lioure, B.
AU - Desablens, B.
AU - Pignon, B.
AU - Abgrall, J. P.
AU - Leporrier, M.
AU - Dupriez, B.
AU - Guyotat, D.
AU - Lepelley, P.
AU - Fenaux, P.
PY - 1998/9/15
Y1 - 1998/9/15
N2 - 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 ≤ 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.
AB - 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 ≤ 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.
KW - Intensive chemotherapy
KW - Multidrug resistance
KW - Myelodysplastic syndromes
KW - P glycoprotein
KW - Quinine
UR - http://www.scopus.com/inward/record.url?scp=7344227279&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2141.1998.00870.x
DO - 10.1046/j.1365-2141.1998.00870.x
M3 - Article
C2 - 9734653
AN - SCOPUS:7344227279
SN - 0007-1048
VL - 102
SP - 1015
EP - 1024
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -