The state of hepatic artery infusion chemotherapy in the management of metastatic colorectal cancer to the liver

Abstract

Rationale for hepatic artery infusion (HAI) chemotherapyThere are approximately 150,000 new cases of colorectal carcinoma diagnosed annually in the United States (1). Approximately 25% of patients present with metastatic disease at the time of diagnosis (2) and over 50% will develop metastasis to the liver at some point in their lifetime (3). Five-year overall survival (OS) in metastatic colorectal cancer (CRC) confined to the liver is approximately 20%, although complete resection can increase 5-year survival to over 50% in selected series (4-7).Liver resection provides the only chance for cure in patients with colorectal liver metastases (CRLM), however, only 15-20% of patients with CRC metastases confined to the liver are deemed resection candidates at presentation. Most patients with CRC die from metastatic disease, and two-thirds of CRC deaths are due to liver metastases (8).For patients with initially unresectable CRLM, regional treatment of metastatic disease has been a topic of considerable interest given the underwhelming response rates to systemic chemotherapy alone with median survival of roughly 20 months (9). First line systemic chemotherapy for metastatic CRC includes a fluoropyrimidine combined with other agents in various schedules (10). Despite the advances of modern combination regimens [e.g., 5-FU/ leucovorin/oxaliplatin (FOLFOX), 5-FU/leucovorin/ irinotecan (FOLFIRI) and 5-FU/leucovorin/oxaliplatin/ irinotecan (FOLFOXIRI) and targeted therapies including anti-epidermal growth factor receptor (EGFR) for RAS wild-type tumors, and anti-vascular endothelial growth

The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy

“…Instead of systemic therapy, hepatic arterial infusion (HAI) therapy, a locoregional high-dose liver-directed chemotherapy, can also be applied for patients with initially unresectable liver metastases. In this regard, HAI is applied during surgical laparotomy with an insertion of a catheter into the gastroduodenal artery, which remains the gold standard to date [142]. Although HAI has been associated with improved survival [143], patients with CRLM harboring p53 mutations were more resistant to hepatic arterial chemotherapy with floxuridine (fluorinated pyrimidine) [144].…”

Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist

“…NCCN guidelines consider CI as an option of treatment in resectable and unresectable LMCRC, but it should be considered selectively and only at institutions with experience in this procedure. It is an acceptable first-line option in the United States for unresectable LMCRC and a treatment option in the adjuvant treatment, but it remains infrequently used [ 177 , 178 ]. However, ESMO guidelines do not recommend CI [ 5 ].…”