A phase II study of intensive chemotherapy with fludarabine, cytarabine, and mitoxantrone in P glycoprotein-negative high-risk myelodysplastic syndromes.
Since leukemic cells primed by exposure to fludarabine exhibit enhanced accumulation of cytarabine triphosphate (the cytotoxic nucleotide of cytarabine), especially with continuous cytarabine (AraC) infusion, a phase II trial was designed to explore the feasibility and efficacy of a combination chemotherapy associating fludarabine, mitoxantrone (MXN), and high-dose cytarabine (continuous infusion) for high-risk P glycoprotein (PGP)-negative myelodysplastic syndromes (MDS) (FAM protocol). The outcomes of FAM-treated patients were compared with those of 32 PGP-negative MDS patients fulfilling identical inclusion and response criteria treated with MXN+AraC (1 g/m(2)/12 h d(1-5), MA protocol). A total of 29 patients (median age 55 years) were included in the FAM group. Six (21%) died from the procedure, and 16 (55%) achieved complete remission (CR). Of these, nine received consolidation chemotherapy, five were autografted and two were allografted in first CR. Abnormal karyotype was the only factor associated with poor survival. The overall median follow-up was 10.9 months. There was no significant difference between FAM and MA protocols with respect to CR rate, treatment-related mortality, duration of leukopenia, neutropenia, autologous stem cell transplantation feasibility, relapse-free survival, or overall survival. The duration of thrombocytopenia was significantly longer in the FAM protocol. In conclusion, the present results suggest that the combination therapy of fludarabine, MXN, and high-dose AraC does not improve CR rate, survival, or disease-free survival in high-risk MDS.
Prébet
Thomas
T
Service d'Hématologie, Pavillon E, CHU, Hôpital Edouard Herriot, Lyon, France.
Ducastelle
Sophie
S
Debotton
Stephan
S
Stamatoullas
Aspasia
A
Deconinck
Eric
E
Fruchart
Christophe
C
Gratecos
Nicole
N
Ifrah
Norbert
N
Dreyfus
François
F
Fenaux
Pierre
P
Wattel
Eric
E
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009190:Myelodysplastic Syndromes / Q000145:classification / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D013997:Time Factors; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003561:Cytarabine; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine