SDX-105 (Treanda™) Enhances the Tumor Growth Inhibitory Effect of Rituximab in Daudi Lymphoma Xenografts.

SDX-105 (Treanda™, Bendamustine HCl), a structurally and mechanistically unique multifunctional anticancer drug, has been demonstrated to be more potent than other 2-chloroethylamine alkylators in a variety of cell lines resistant to traditional alkylating agents. We previously reported that SDX-105 inhibits growth of SUDHL-1 and Daudi human lymphoma tumor xenografts in SCID mice in a dose-dependent manner (AACR PROC 45: Abs #4575). The current studies examine whether SDX-105 in combination with rituximab confers better efficacy. Daudi cells (1.0 X 10⁷ cells/mouse) were inoculated s.c. in the flanks of SCID mice. After the tumors reached approximately 100 mm³, SDX-105 (10 mg/kg/d i.p., d 0–4), rituximab (75 mg/kg/d i.v., d 0, 2, 4) or both (same respective doses and treatment days) were administered; a second cycle of treatment was subsequently initiated on day 28. Tumor growth and body weight were monitored for 60 days. On day 20, mean tumor volumes were 2118, 847, 511 and 221 mm³ for the control, rituximab, SDX-105 and the combination group, respectively. Tumors in treated groups were significantly smaller than tumors in the control group, and the tumors in the combination group were significantly smaller than tumors in the rituximab group (p <0.02). In the combination group, the antitumor effect was sustained up to day 60 and there was one ‘cure’ (non palpable). There was no body weight loss in the control or rituximab group; 10% body weight loss was observed in SDX-105 and the combination groups. These results corroborate our previous in vivo single agent data in this model and provide further support for the use of SDX-105 with rituximab in clinical trials.