In the treatment of B-cell non-Hodgkin lymphoma (B-NHL), rituximab improves long-term survival in combination with conventional chemotherapy. However, because the majority of B-NHL patients eventually relapse, the development of more effective therapies is needed. This study evaluated the antitumor effects of a combination treatment involving sepantronium bromide (YM155), a first-in-class survivin suppressant, and rituximab in B-NHL xenograft mouse models. In DB, WSU-DLCL-2, and Mino xenograft-bearing mice, the combination treatment of YM155 and rituximab induced significant tumor growth inhibition and tumor regression compared with either agent alone. On day 3 after the initiation of treatment, a significant decrease in both 18F-FDG and 18F-FLT tumor uptake from pretreatment levels was observed in combination treatment groups. The Ki-67 proliferation index was significantly decreased on day 3 in the xenograft models treated with combination treatment, suggesting that the combination of YM155 plus rituximab reduced cell proliferation as well as glucose metabolism. These findings demonstrate that YM155 and rituximab combination treatment enhances antitumor activity in B-NHL xenografts, and that 18F-FLT- and 18F-FDG-PET imaging may allow the early functional evaluation of treatment responses in patients with B-NHL.
See article at J Pharmacol Exp Ther 2012, 343:178–183.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics