Abstract 809: A novel woodchuck model of hepatic artery infusion (HAI) with FACT complex targeted drug CBL0137

Abstract

Abstract Background: The liver has unique anatomy in that most blood flow to normal hepatocytes is derived from the portal venous system, while liver tumors obtain their nutrient blood supply exclusively from the hepatic artery. Hepatic artery infusion (HAI) concentrates chemotherapy agents delivering them directly to the tumor bed with the first-pass effect. Although, HAI chemotherapy as a regional therapy has been used clinically for decades in the treatment of both primary and metastatic cancers of the liver, significant toxicity remains a concern, and clinical results have been mixed. The purpose of this study was to establish preclinical HAI model in a woodchuck and administer the FACT (facilitates chromatin transcription) complex targeted drug CBL0137. Material and methods: Woodchuck hepatitis virus infected Eastern Woodchucks (Marmota monax) were used for the study. Hepatocellular carcinoma (HCC) developed spontaneously about 18 months after birth. The size of HCC was monitored with ultrasound every 2 weeks, and 4 woodchucks bearing over 2 cm tumors were used for the experimental group. Prophylactic cholecystectomy was performed first, and then a 2Fr. (ID=0.012”, OD=0.025”) vascular access port (VAP) was implanted in the gastroduodenal artery (GDA) after collateral vessel ligations. HAI was performed at room temperature via a VAP using 15mg/kg of CBL0137 at a volume of 3 mL/kg for 30 minutes, and tumor responses were investigated with MRI on day 0 (the surgery day of HAI port) and day 7 after HAI. Results: Anatomy variations existed in the size and location of the supraduodenal artery or pancreatico-duodenal artery. 4/4 success rate of a port implantation was achieved without mortality, but 1/4 animals suffered post-operative bleeding at the port head site, attributed to coagulopathy secondary to hepatic dysfunction. And, 4/4 animals were partially anorexic for up to 7 days post-surgery. Decreased tumor volume and Ktrans (a measure of capillary permeability) were detected 7 days after single HAI with CBL0137. Conclusion: Although the anticancer effect of CBL0137 on HCC was not clear because of a lack of the control group, we successfully implanted a VAP into the GDA of 4 woodchucks bearing unresectable HCC for HAI. The described woodchuck model may serve as a platform for identifying novel drugs and optimal conditions for the treatment of primary and metastatic liver tumors. Citation Format: Minhyung Kim, Leslie I. Curtin, Colin A. Powers, Sandra Sexton, Katerina V. Gurova, Andrei V. Gudkov, Renuka V. Iyer. A novel woodchuck model of hepatic artery infusion (HAI) with FACT complex targeted drug CBL0137 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 809. doi:10.1158/1538-7445.AM2017-809