Journal Article

The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome

Hunter, A, Yin, J, Cahalin, P, Craig, J, Hills, R K, Russell, N, Burnett, A K, Milligan, D, Wheatley, K, Kell, J, McMullin, M-F, Bowen, D

2011

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/92/436/108 / 692/699/67/1990/283/1897 / 692/700/1518 / 692/700/565/1436/1437 / Acute myeloid leukemia / Aged / Aged, 80 and over / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Arsenic / Arsenic Trioxide / Arsenicals - administration & dosage / Arsenicals - adverse effects / Biological and medical sciences / Cancer Research / Chemical and Drug Induced Liver Injury - etiology / Chemotherapy / Chemotherapy, Combination / Comorbidity / Critical Care Medicine / Cytarabine - administration & dosage / Cytarabine - adverse effects / Disease-Free Survival / Early Termination of Clinical Trials / Female / Gastrointestinal Diseases - chemically induced / Health aspects / Heart Diseases - chemically induced / Hematologic and hematopoietic diseases / Hematology / Humans / Intensive / Internal Medicine / Kaplan-Meier Estimate / Leukemia / Leukemia, Myeloid, Acute - drug therapy / Leukemia, Myeloid, Acute - mortality / Leukemia, Myelomonocytic, Acute / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Male / Medical sciences / Medicine / Medicine & Public Health / Middle Aged / Myelodysplastic syndrome / Myelodysplastic syndromes / Oncology / original-article / Oxides - administration & dosage / Oxides - adverse effects / Remission / Remission Induction / Survival / Toxicity / Treatment Outcome