Abstract 3661: Vascular changes and potentiating secondary drug delivery in colorectal cancer with Irinophore C

Introduction: Colorectal cancer is the third most common cancer in the world. The predominant chemotherapeutic treatment in CRC is a combination of 5-fluorouracil (5-FU) and irinotecan (CPT-11). However, the combination is limited by toxicity and resistance. We now report on the effects of 5-FU in combination with a liposomal formulation of CPT-11, Irinophore C, that is more efficacious and less toxic than free CPT-11. Materials and Methods: 5-FU was used singly and in combination with Irinophore C in a subcutaneous model of colorectal cancer, HT-29, to assess therapeutic efficacy and toxic effects. 5-FU and Irinophore C (40mg/kg) were injected intravenously on a Q7Dx3 schedule, and tumor growth delay was measured. In a subsequent study, a single bolus injection of 14 C-spiked 5-FU was delivered at different timepoints during Irinophore C (tritium-labeled) or saline treatment (Q7Dx3), and the accumulation of 5-FU in tumor tissue measured with scintigraphy. Tumors were also harvested and snap-frozen at early (days 1 - 7) and late (days 14 and 21) time points following Irinophore C treatment. Cryosections were subsequently examined for perfusion using the fluorescent dye Hoechst 33342, stained for apoptosis (TUNEL), CD31, CD105, Collagen IV and with HE 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3661.