Arsenic Trioxide and Ascorbic Acid is Tolerable and Active in Myelodysplastic Syndrome, Study Shows
According to research presented at the 51st Annual Meeting and Exposition of the American Society of Hematology in New Orleans, the combination of arsenic trioxide (ATO) and ascorbic acid is tolerable and active in about 25% of myelodysplastic syndrome (MDS) patients.
Arsenic trioxide inhibits angiogenesis and induces apoptosis and differentiation in variety of malignant cells. Italian researchers conducted a multicenter phase II study with a combination of arsenic trioxide and ascorbic acid in MDS patients. Patient eligibility included those with 3q26 rearrangement or high EVI-1 levels; non-RAEB patients at low-intermediate/1 risk who failed a previous therapy; and RAEB or high-intermediate-2 risk patients not eligible to chemotherapy and/or bone marrow transplant.
Forty-four patients with median age of 71 years (range 47–80) were enrolled. Arsenic trioxide was administrated intravenously over one hour at the loading dose of 0.30 mg/kg/day for five consecutive days, followed by 0.25 mg/kg/day twice weekly for 15 weeks. Ascorbic acid 1000 mg was given IV within 30 minutes after each arsenic trioxide infusion. Response evaluation was scheduled after two and four months of treatment according to the IWG criteria.
Ten out of the 44 evaluable patients obtained a response (23%). They included one complete remission, two major erythroid hematologic improvement (HI-E major), three minor HI-E, two major neutrophil improvemet (HI-N), and two major trilineage responses. The response rate was 35% in lower risk IPSS patients and 6% in higher risk pts (P=0.05).Only three pts with high EVI-1 expression achieved a response. In eight out of 10 responders, the response was evident within the first eight weeks of treatment. Twenty three (52%) patients discontinued treatment because of disease progression (11%), severe adverse events (32%), drug-unrelated adverse events (5%), or withdrawal of consent (5%). Severe neutropenia and thrombocytopenia were observed respectively in 45% and 23% of patients. The other G3-4 adverse events observed were ATRA-like syndrome (9%), cardiotoxicity (11%), infection (11%), and hepatotoxicity (9%). No toxic death was observed.