A study by Zhu Chen of the Shanghai Institute of Hematology and an international group from the University of Paris and the Mount Sinai School of Medicine in New York published in the April 2004 edition of the Proceedings of the National Academy of Sciences (PNAS), concluded that the combination of arsenic trioxide and ATRA induction therapy resulted in faster time to achieve complete remission (CR) and longer lasting remissions than either of the two drugs used alone. Sixty-one newly diagnosed APL patients were randomized into three treatment groups; single agent ATRA, single agent arsenic trioxide, or the combination of the two.

Though CR rates in all groups were high (>90 per cent), the leukemia burden at time of CR decreased more significantly in the combined therapy group compared to the mono-therapy arms. Importantly, all 20 cases in the combination group remained in CR after a median follow up of 18 months, whereas, seven of the 37 patients (19 per cent) treated with mono-therapy relapsed. Studies at the molecular level demonstrated that the combination was 17.7 times more effective at eliminating leukemic cells than with ATRA alone and 3.7 times more effective than with arsenic trioxide alone.

"Standard induction treatment for front line APL currently consists of ATRA plus an anthracycline chemotherapy which results in a high rate of remission and cure. While very effective in eradicating this particular leukemia, anthracyclines are unfortunately associated with substantial short-term toxicities including hair loss, neutropenia, infections and mucositis. More importantly, for the large proportion of APL patients that are cured, the large doses of anthracyclines used are associated with an increased lifetime risk for developing secondary leukemias and myelodysplastic syndromes and may cause permanent impairment in heart function," explained Jack W. Singer, Chief Medical Officer at CTI. "Given the preliminary experience of this study, we're moving quickly to conduct our own clinical trial to determine if Trisenox can replace the requirement for an anthracycline in the induction treatment of patients with newly diagnosed APL."