Arsenic advantages

A study by Zhu Chen of the Shanghai Institute of Haematology and an international group from the Univer-sity 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 Arsenic Trioxide in Combination with All-Trans Retinoic Acid (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 Acute Promyelocytic Leukaemia (APL) patients were randomised 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%), the leukaemia burden at time of CR decreased more significantly in the combined therapy group compared with the monotherapy 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%) treated with monotherapy relapsed. Studies at the molecular level demonstrated that the combination was 17.7 times more effective at elimi-nating leukaemic cells than with ATRA alone and 3.7 times more effective than with arsenic trioxide alone. Cell Therapeutics markets Trisenox (arsenic trioxide) injection in the United States and Europe.

'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 leukaemia, 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 leukaemias and myelodysplastic syndromes and may cause permanent impairment in heart function,' explained Dr Jack 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.'