Chemoembolization for Colorectal Liver Metastases after FOLFOX Failure

Abstract

Colon carcinoma remains the third most common cancer in the United States among men and women, and accounts for 9% of all cancer deaths (1). The majority (50%–60%) of patients with colon cancer will eventually develop liver metastases, and 80%–90% of these individuals will present with unresectable disease. Liver metastases remain the most common cause of mortality in these patients, and they are therefore the focus of many current therapies. The oncologic rationale for transarterial chemoembolization of colorectal metastases shares similarities with transarterial chemoembolization performed for hepatocellular carcinoma and other chemoembolic-responsive tumor pathologic proceses. A high first-pass effect of cytotoxic agents, augmented by prolonged intracellular drug levels from embolic effects on tumor vasculature, produces a high rate of local response. However, in the United States, a relative paucity of data to support chemoembolization for colorectal metastases has limited broader use. Limited prospective data of transarterial chemoembolization for colon metastases have led some third-party payors to decline reimbursement, citing that the therapy is still considered investigational or experimental. The most recent treatment guidelines of the National Comprehensive Cancer Network (2) consider arterially directed therapies such as chemoembolization a ‘‘category 3’’ recommendation (ie, major disagreement that the intervention is appropriate) based on insufficient data and variations in techniques among institutions. Several retrospective studies performed in the 1990s in the United States suggested that transarterial chemoembolization extends survival time in patients with colorectal metastases without significant toxicity. These include the Puget Sound Oncology Group (3) and Northwestern University studies (4). The patients in these studies were not naive to systemic chemotherapy, and response rates of 63%–70% were observed, with median survival times of 14–29 months. These studies added to previous encouraging results during a time when median survival for patients with metastatic colon carcinoma to the liver was 8–12 months with conventional 5-fluorouracil (5-FU)/ leucovorin chemotherapy (5,6). Since that time, the paradigm of chemotherapy for these patients has significantly changed. The response rates to first-line chemotherapy with 5-FU/leucovorin/oxaliplatin (FOLFOX) and 5-FU/leucovorin/irinotecan (FOLFIRI) have increased to 50%–65%, compared with 30% for 5-FU/leucovorin (2). In addition, incremental benefits of the addition of biologic therapies such as bevacizumab, cetuximab, and panitumumab to cytotoxic regimens have extended survival times even further. The number of treatment algorithms supported by randomized trials has increased treatment options for patients who show disease progression with firstor second-line therapies or develop drug-related toxicities (7–11). Nevertheless, there remains an important subset of patients who show disease progression or recurrence after sequential systemic therapies, and transarterial therapies have the potential to further improve survival outcomes while maintaining quality of life. More recent experience with transarterial chemoembolization from the author’s institution (12), which achieved a median survival of 27 months, indicates that salvage therapy for metastatic colon carcinoma continues to hold promise. Other transarterial therapies have emerged in the past decade that are gaining broader acceptance for colon metastases, particularly yttrium-90 radioembolization. Although radioembolization was initially used as salvage therapy for patients following sequential chemotherapy (13,14), several prospective randomized trials are under way to evaluate the incremental benefit of radioembolization administered concurrently with firstor second-line chemotherapy. Technologic improvements in transarterial chemoembolization have also emerged through the use of drug-eluting beads. These agents may enable transarterial chemoembolization to become better tolerated by patients and provide more controlled drug delivery to tumor cells while using cytotoxic agents with higher response rates (eg, The author has not identified a conflict of interest. From the Section of Interventional Radiology, Department of Radiology, University of Pennsylvania School of Medicine, Penn Presbyterian Medical Center, 39th and Market Sts., Philadelphia, PA 19104. Received October 15, 2012; accepted October 16, 2012. Address correspondence to T.W.I.C.; Email: timothy.clark@uphs.upenn.edu