title: Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein: results of a randomized study.
abstract: 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.
authors.affiliation: Groupe Français des Myélodysplasies, Service des Maladies du Sang, CHU, Lille, France.
authors.forename: E
authors.initials: E
authors.lastname: Wattel
authors.forename: E
authors.initials: E
authors.lastname: Solary
authors.forename: B
authors.initials: B
authors.lastname: Hecquet
authors.forename: D
authors.initials: D
authors.lastname: Caillot
authors.forename: N
authors.initials: N
authors.lastname: Ifrah
authors.forename: A
authors.initials: A
authors.lastname: Brion
authors.forename: B
authors.initials: B
authors.lastname: Mahé
authors.forename: N
authors.initials: N
authors.lastname: Milpied
authors.forename: M
authors.initials: M
authors.lastname: Janvier
authors.forename: A
authors.initials: A
authors.lastname: Guerci
authors.forename: H
authors.initials: H
authors.lastname: Rochant
authors.forename: C
authors.initials: C
authors.lastname: Cordonnier
authors.forename: F
authors.initials: F
authors.lastname: Dreyfus
authors.forename: A
authors.initials: A
authors.lastname: Buzyn
authors.forename: L
authors.initials: L
authors.lastname: Hoang-Ngoc
authors.forename: A M
authors.initials: AM
authors.lastname: Stoppa
authors.forename: N
authors.initials: N
authors.lastname: Gratecos
authors.forename: A
authors.initials: A
authors.lastname: Sadoun
authors.forename: A
authors.initials: A
authors.lastname: Stamatoulas
authors.forename: H
authors.initials: H
authors.lastname: Tilly
authors.forename: P
authors.initials: P
authors.lastname: Brice
authors.forename: F
authors.initials: F
authors.lastname: Maloisel
authors.forename: B
authors.initials: B
authors.lastname: Lioure
authors.forename: B
authors.initials: B
authors.lastname: Desablens
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D011803:Quinine / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009363:Neoplasm Proteins; D003561:Cytarabine; D011803:Quinine; D008942:Mitoxantrone