Hepatic arterial infusion with nanoliposomal irinotecan leads to significant regression of tumor size of colorectal liver metastases in a CC531 rat model

Abstract

Long-term therapy for unresectable colorectal liver metastases remains challenging. Intraarterial treatments aim to avoid systemic adverse effects of chemotherapy. Nanoliposomal cytotoxic drugs manage to increase the drug concentration within the tumor while reducing toxicity in healthy tissue. In this study we analyzed the effect of hepatic arterial infusion (HAI) with nanoliposomal irinotecan with or without the combination of embolization particles in a rat model for colorectal liver metastases. For the study 32 WAG/Rij rats received subcapsular tumor implantation with CC531 rat colonic adenocarcinoma cells. After ten days tumor size was assessed via ultrasound and animals underwent HAI. One group served as control receiving NaCl 0.9 % (Sham), the three treatment groups received either nanoliposomal irinotecan (HAI nal iri), Embocept® S (HAI Embo) or Embocept® S and nanoliposomal irinotecan (HAI Embo+nal iri). Three days after treatment animals were sacrificed after assessment of tumor size. As a result all treatment groups showed a significant reduction in tumor growth compared to Sham (p<0.05). Expression of the apoptosis marker caspase-3 was enhanced in HAI nal iri and HAI Embo+nal iri compared to Sham and HAI Embo and even significantly enhanced after HAI Embo+nal iri in comparison to Sham (p<0.05). We were able to show that HAI with Embocept® S led to significantly reduced tumor growth while HAI with nanoliposomal irinotecan alone or in combination with Embocept® S even led to a reduction of tumor size. Thus, we demonstrate that intraarterial treatment with nanoliposomal irinotecan effectively inhibits tumor growth in a rat model of colorectal liver metastases and demands further investigation.

Keywords: Colorectal liver metastases; Hepatic arterial infusion; Nanaoliposomal irinotecan.