title: The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome.
abstract: Most patients with acute myeloid leukaemia (AML) are older, with many unsuitable for conventional chemotherapy. Low-dose Ara-C (LDAC) is superior to best supportive care but is still inadequate. The combination of arsenic trioxide (ATO) and LDAC showed promise in an unrandomised study. We report a randomised trial of LDAC versus LDAC+ATO. Patients with AML according to WHO criteria or myelodysplastic syndrome with >10% blasts, considered as unfit for conventional chemotherapy, were randomised between subcutaneous Ara-C (20 mg b.d. for 10 days) and the same LDAC schedule with ATO (0.25 mg/kg) on days 1-5, 9 and 11, for at least four courses every 4 to 6 weeks. Overall 166 patients were entered; the trial was terminated on the advice of the DMC, as the projected benefit was not observed. Overall 14% of patients achieved complete remission (CR) and 7% CRi. Median survival was 5.5 months and 19 months for responders (CR: not reached; CRi: 14 months; non-responders: 4 months). There were no differences in response or survival between the arms. Grade 3/4 cardiac and liver toxicity, and supportive care requirements were greater in the ATO arm. This randomised comparison demonstrates that adding ATO to LDAC provides no benefit for older patients with AML.
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, Heath Park, Cardiff, UK. BurnettAK@Cardiff.ac.uk
authors.forename: A K
authors.initials: AK
authors.lastname: Burnett
authors.forename: R K
authors.initials: RK
authors.lastname: Hills
authors.forename: A
authors.initials: A
authors.lastname: Hunter
authors.forename: D
authors.initials: D
authors.lastname: Milligan
authors.forename: J
authors.initials: J
authors.lastname: Kell
authors.forename: K
authors.initials: K
authors.lastname: Wheatley
authors.forename: J
authors.initials: J
authors.lastname: Yin
authors.forename: M-F
authors.initials: MF
authors.lastname: McMullin
authors.forename: P
authors.initials: P
authors.lastname: Cahalin
authors.forename: J
authors.initials: J
authors.lastname: Craig
authors.forename: D
authors.initials: D
authors.lastname: Bowen
authors.forename: N
authors.initials: N
authors.lastname: Russell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D015897:Comorbidity; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D057239:Early Termination of Clinical Trials; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D015479:Leukemia, Myelomonocytic, Acute; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D001152:Arsenicals; D010087:Oxides; D003561:Cytarabine; D000077237:Arsenic Trioxide