title: Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival.
abstract: Better treatment is required for older patients with acute myeloid leukemia (AML) not considered fit for intensive chemotherapy. We report a randomized comparison of low-dose Ara-C (LDAC) vs the novel nucleoside, clofarabine, in untreated older patients with AML and high-risk myelodysplastic syndrome (MDS). A total of 406 patients with de novo (62%), secondary disease (24%), or high-risk MDS (>10% marrow blasts) (15%), median age 74 years, were randomized to LDAC 20 mg twice daily for 10 days every 6 weeks or clofarabine 20 mg/m(2) on days 1 to 5, both for up to 4 courses. These patients had more adverse demographics than contemporaneous intensively treated patients. The overall remission rate was 28%, and 2-year survival was 13%. Clofarabine significantly improved complete remission (22% vs 12%; hazard ratio [HR] = 0.47 [0.28-0.79]; P = .005) and overall response (38% vs 19%; HR = 0.41 [0.26-0.62]; P < .0001), but there was no difference in overall survival, explained by poorer survival in the clofarabine patients who did not gain complete remission and also following relapse. Clofarabine was more myelosuppressive and required more supportive care. Although clofarabine doubled remission rates, overall survival was not improved overall or in any subgroup. The treatment of patients of the type treated here remains a major unmet need.
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom. burnettak@cardiff.ac.uk.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Burnett
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Russell
authors.forename: Ann E
authors.initials: AE
authors.lastname: Hunter
authors.forename: Donald
authors.initials: D
authors.lastname: Milligan
authors.forename: Steven
authors.initials: S
authors.lastname: Knapper
authors.forename: Keith
authors.initials: K
authors.lastname: Wheatley
authors.forename: John
authors.initials: J
authors.lastname: Yin
authors.forename: Mary F
authors.initials: MF
authors.lastname: McMullin
authors.forename: Sahra
authors.initials: S
authors.lastname: Ali
authors.forename: David
authors.initials: D
authors.lastname: Bowen
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hills
mesh_terms: D000227:Adenine Nucleotides / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000627:therapeutic use*; D000077866:Clofarabine; D003561:Cytarabine / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000401:mortality; D016016:Proportional Hazards Models; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D003561:Cytarabine; D000077866:Clofarabine