FEASIBILITY OF SALVAGE CHEMOTHERAPY FOR REFRACTORY OR RELAPSED NON-HODGKINS-LYMPHOMA WITH 2 TOPOISOMERASE-II INHIBITORS, MST-16 AND VP-16

A feasibility study was carried out on the treatment for refractory an d relapsed non-Hodgkin's lymphomas with a combination of two oral topo isomerase II inhibitors, MST-16 and VP-16. On the basis of the synergi stic activity in preclinical studies and the schedule dependency in th ese drugs, low-dose and long-term administration was planned. For the anticipated myelosuppression, two different regimens were designed as an open label trial in this study. In Regimen I, 400 mg of MST-16 comb ined with 25 mg of VP-16 was administered daily. With this regimen, th e response rate (RR)/median time to tumor progression (TTP) in all eva luable patients was 50% (2/4)/8.5 months in low grade (indolent) lymph oma and 60% (6/10)/5.2 months in intermediate/high grade (aggressive) lymphomas. In Regimen II, 400 mg of MST-16 combined with 25 mg of VP-1 6 was administered intermittently (3 days a week or every other day). With this regimen, there was an RR/median TTP of 60% (3/5)/7.0 months in indolent lymphoma and 33.3% (4/12)/1.1 months in aggressive lymphom a. A major side effect in both of these regimens was myelosuppression, with the incidence of grades 3 and 4 toxicity being higher in Regimen I than in Regimen II. The other side effects were uncommon and not se vere. These findings indicated that two regimens were tolerated well a nd were promising for refractory and relapsed aggressive non-Hodgkin's lymphomas. To define the anti-tumor activity and safety of these regi mens precisely, large-scale prospective randomized trials are necessar y.