Role of Hepatic Artery Infusion Pump Chemotherapy for Unresectable Colorectal Cancer Liver Metastases

Although liver metastasis develops in over half of patients with colorectal cancer, only 15–20% of these patients are resectable at presentation. Moreover, patients with unresectable colorectal liver metastasis (CRLM) who progress on first-line systemic chemotherapy have limited treatment options. Hepatic arterial infusion chemotherapy (HAIC), in combination with systemic chemotherapy, leverages a multimodality approach to achieving hepatic disease control and/or expanding resectability in patients with liver-dominant disease. Intra-arterial delivery of agents with high first-pass hepatic extraction (e.g., floxuridine [FUDR]) limits systemic toxicity and allows for administration of systemic chemotherapy at near-full doses. HAIC in conjunction with systemic chemotherapy augments response rates up to 92% in chemotherapy-naive, and up to 85% in pretreated, patients with unresectable CRLM. In turn, these responses translate into encouraging rates of conversion to resectability (CTR). Prospective trials of HAIC have reported CTR rates as high as 52% in heavily pretreated patients with extensive hepatic disease burden. As such, CTR is a compelling indication for liver-directed chemotherapy in this subset of patients. This chapter discusses the rationale for HAIC, evolution of rational combinations with systemic chemotherapy, contemporary evidence for CTR using HAIC and systemic chemotherapy, juxtaposition with CTR rates using systemic chemotherapy alone, and the morbidity and toxicity profiles of HAI chemotherapy. Finally, the argument is made for consideration of both earlier initiation of HAIC in chemotherapy-naive patients with unresectable CRLM and adoption of HAIC strategies to augment resectability rates in patients who have failed first-line systemic chemotherapy before proceeding to second-/third-line regimens.