Clinical trials for malignant lymphoma in Japan.

The results of the clinical trials by the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG-LSG) and those of the industry-supported trials mainly conducted by the members of JCOG-LSG are summarized. In the treatment of advanced aggressive non-Hodgkin's lymphoma (NHL), we investigated the efficacy of granulocyte colony-stimulating factor (G-CSF)-supported, dose-intensified strategies. Based on the results of a randomized phase II study (JCOG9505), we conducted a phase III study, JCOG9809, comparing CHOP and biweekly CHOP. However, JCOG9809 was terminated early based on the results of a planned interim analysis, because it was deemed highly unlikely that biweekly CHOP would be superior to standard CHOP. For aggressive ATL, a G-CSF-supported, dose-intensified, multi-agent regimen (JCOG9303; LSG15) showed superior efficacy to our historical controls. To establish a new standard for ATL, we conducted a phase III study, JCOG9801, comparing LSG15 and biweekly CHOP. To develop new agents for lymphoid malignancies, we focused on irinotecan hydrochloride, interferon-alpha, cladribine and oral fludarabine. Among them, cladribine and oral fludarabine are promising for indolent B-cell malignancies. The Japanese phase I and II studies of rituximab, a chimeric anti-CD20 monoclonal antibody, in relapsed indolent and aggressive B-NHL showed high efficacy with minimal toxicities, which led us to conduct combination studies with chemotherapy for B-NHL. In addition, a phase I study of a radiolabeled anti-CD20 antibody (ibritumomab tiuxetan) was completed in 2003, and a phase II study for indolent B-NHL will be initiated. The multicenter trials by the JCOG-LSG and industry-supported new agent studies will contribute to further improvement in the treatment of malignant lymphoma.