Abstracts of Clinical Meeting on 12-July-2002
Phase I / II Study of Arsenic Trioxide in Patients with Multiple Myeloma
Steve Schey, Consultant Haematologist, Guy's & St Thomas' NHS Trust, London, SE1 9RT
Arsenic Trioxide (ATO) inhibits growth, reduces viability and induces apoptosis in Myeloma cell lines at pharmaceutical concentrations, but has not been shown to affect T, myeloid or epithelial cell lines in vivo. It has also been shown to reduce plasma cell differentiation in normal B cells. It may be active against myeloma cells that express the MDR gene as preliminary data has shown increased cell death in doxorubicin resistant human leukaemia and myeloma cells exposed to ATO.
Preliminary studies in a group of 14 patients with advanced refractory multiple myeloma, who have been heavily pre-treated including 7 who have had previous autologous stem cell transplantation. All had been treated with a salvage regime with dexamethasone, cyclophosphamide, etoposide and cisplatin followed by thalidomide and had shown progressive disease. All 14 had cytogenetic abnormalities, including 8 who had deletion of chromosome 13. In preliminary (unaudited) results 5 patients had a decrease in paraprotein on therapy and a further 5 had stabilisation of paraprotein after a period on treatment varying from 7 to 78 days with daily dosing.
The study aims to determine the rate of clinical response following treatment with ATO in patients who have relapsed from or who are refractory to conventional therapies for myeloma. Patients will be eligible for the study if they have a confirmed diagnosis of myeloma and have relapsed from or are refractory to <3 prior therapies.
Treatment will comprise of ATO loading doses administered daily for 5 days as an infusion and maintenance doses twice weekly after this for a maximum of 16 weeks. Patients whose disease is stable after this period can continue on therapy as long as clinical benefit is obtained and those whose disease responds can continue on therapy until 4 weeks after complete remission is documented.
The study will be recruiting a total of 55 patients from a variety of centres internationally.