The Addition of Arsenic Trioxide to Low Dose Ara-C in Older Patients with AML Does Not Improve Outcome

BACKGROUND: Most patients with acute myeloid leukaemia 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 un-randomised study. We report a randomised trial of LDAC versus LDAC+ATO. METHODS: Patients with AML according to WHO criteria or myelodysplastic syndrome with >10% blasts, considered unfit for conventional chemotherapy, were randomised between subcutaneous ara-c (20mg b.d. for 10 days) and the same LDAC schedule with ATO (0.25mg/kg) on days 1-5,9,11, for at least 4 courses every 4 to 6 weeks. Overall 166 patients were entered; the trial was terminated on the advice of the DMC since the projected benefit was not observed. RESULTS: 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. CONCLUSIONS: This randomised comparison demonstrates that adding ATO to LDAC provides no benefit for older patients with AML.