SDX-105 (Bendamustine) inhibits growth of SU-DHL-1 and Daudi lymphoma xenografts in SCID mice

Abstract

4575 SDX-105 is a structurally and functionally unique anticancer agent and has been demonstrated to be effective and relatively more potent in vitro than other alkylators in a variety of cell lines resistant to traditional alkylating agents. We now report SDX-105 inhibits growth of SU-DHL-1 and Daudi lymphoma tumor xenografts in SCID mice. SU-DHL-1 or Daudi cells (6.5 X 106 or 1.0 X 107 cells per mouse, respectively) were inoculated subcutaneously into the flanks of SCID mice. After the tumors reached approximately 100 mm3, mice were administered SDX-105 (2 to 32 mg/kg/d i.p. for 5 days), and tumor growth and body weight were monitored for 28 days. SDX-105-treated mice showed dose- and time-dependent tumor growth inhibition compared to untreated controls in both tumors: Daudi tumor volumes in SDX-105-treated (15 mg/kg/d) mice on day 7, 14 and 21 were 124+/−15, 106+/−25 and 212+/−46 mm3 respectively. Control tumors grew relatively faster: the respective tumor volumes were 272+/−13, 712+/−94 and 1428+/−176 mm3. Tumor growth inhibition in SU-DHL-1 xenografts was effective as well: tumor volumes in SDX-105-treated (16 mg/kg/d) mice on day 6, 13 and 20 were 155+/−30, 256+/−77 and 509+/−146 mm3 respectively. The respective control tumor volumes were 443+/−79, 1031+/−85 and 1725+/−129 mm3. There was a significant body weight loss and a few mortalities at doses of 20 mg/kg/d and higher. Cyclophosphamide at a four fold higher dose (60 mg/kg/d) showed tumor growth inhibition comparable to that of SDX-105 (15 mg/kg/d). These data corroborate our previous in vitro efficacy data and provide the first in vivo evidence for its efficacy in human lymphoma xenografts.