5448

INTRODUCTION: A strong need exists for new therapeutic strategies for high grade glioma. While BCNU has been the best performing chemotherapy for this indication, toxicity limits systemic dose. Local BCNU delivery techniques have been attempted to overcome toxicity limitation, however, efficacy has been limited due to insufficient drug levels over the entirety of the tumor. Solvent facilitated perfusion (SFP) after intratumoral (IT) injection may overcome these limitations. We evaluated BCNU dissolved in ethanol (EtOH) (DTI-015) and BCNU dissolved in 50%EtOH/50%PEG in C26, an aggressive, chemo-resistant mouse colorectal tumor. METHODS: Female Balb/c mice of mean body weight (BW) 18.0 0.9 g were implanted subcutaneously with C26 tumor fragments from in vivo passage, and divided into treatment groups (see Table). Caliper-based tumor measurements and BWs were recorded 3 times per week. Mice that experienced complete tumor regression (no palpable mass) that persisted over at least 3 weeks to the study end (86 days) were designated as cures. RESULTS AND DISCUSSION: EtOH or EtOH/PEG vehicles alone had little effect on tumor growth. Systemic BCNU at a dose of 1mg was toxic in all mice (Group 8). IT delivery of 0.5mg of BCNU in both solvent types (Groups 3, 6) produced a 100% cure rate, and only moderate toxicity (<10% mean BW loss in each group). IT delivery of 1mg of BCNU in EtOH (Group 4) and EtOH/PEG (Group 7) was toxic in 2/8 and 3/8 mice respectively, but resulted in cures in remaining mice in these groups (see Table). CONCLUSION: IT delivery of 0.5 mg BCNU in EtOH or EtOH/PEG provides cures in subcutaneous C26 xenografts, with significantly reduced toxicity compared with systemic delivery. The two solvent types performed similarly in terms of toxicity and efficacy.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]