Irinotecan-Eluting 75-150-µm Embolics Lobar Chemoembolization in Patients with Colorectal Cancer Liver Metastases: A Prospective Single-Center Phase I Study
Interventional oncologists have long been involved in treatment of hepatic metastatic disease from colorectal cancer, offering ablation, radioemboliztion, and bland/chemoembolization. Given the propensity of disease, colorectal cancer is number three cause of cancer related death in the US with 60% of patients developing liver metastases at some point, this remains a great interest to IO’s despite transarterial therapy being third line therapy at best. This single center prospective trial evaluates feasibility and safety of using a smaller embolic bead, 75-150 µm, with irinotecan, an established chemotherapeutic for patients who have failed 5-FU therapies While the primary end-points are relatively modest, the group also evaluated treatment efficacy, irinotecan pharmacokinetics, and angiogenesis biomarkers. Ultimately, 14 patients with liver dominant colorectal cancer metastatic disease who had progressed through at least 1 line of systemic therapy were treated. Treatment cycles were 6 weeks, and a patient could be treated twice prior to initial follow up imaging. A maximum of 4 treatment cycles were performed. Retreatment was based on presence of new disease, progression of disease, or stable disease on follow up imaging. The study used 1 vial of LC Bead M1 loaded with 100 mg of irinotecan infused in a lobar manner. Embolization was stopped prior to complete dose delivery if 2-5 heart beat stasis was achieved.
Feasibility was defined as the ability to deliver the entire dose to 80% of the patients. Procedural complications and 30-day adverse events were recorded to determine safety. All 32 embolizations in the 14 patients were completed with delivery of the entire dose each time. There were no procedural complications. The most common 30-day adverse event was abdominal pain, seen in 50% of the patients, with 28.6% qualifying as a severe (grade 3-4). Median overall survival from the first treatment was 18.1 months with 1 year survival of 65%. By EASL criteria, 3 patients had partial response, 4 patients had stable disease, and 6 patients had progression.
Figure 1. (a) Partial response demonstrated in 2 patients based on EASL criteria. On contrast-based imaging (venous phase), the tumor measurements before and after transarterial chemoembolization were, respectively, 3.44 x 3.11 cm and 1.90 x 2.49 cm for patient 1 (71 year old male) and 3.99 x 3.68 cm and 1.47 and 1.37 cm for patient 2 (58 year old male). (b) Kaplan-Meier curves demonstrating MOS and 1-year survival.
While chemoembolization, specifically with irinotecan, has been relatively well studied from 2006 to present, both as third line or salvage treatment and in conjunction with systemic chemotherapy, there has been little research involving smaller sized beads. The advantages of smaller embolics include more distal penetration into the tumor bed and ability for more uniform coverage throughout the target zone. Despite the small number of patients, this data supports the existing data that chemoembolization using 75-150 µm embolics is indeed safe and feasible. Obviously, this study is limited do to sample size, short follow up interval, and hetereogenous pre-existing and subsequent cancer therapies. While this adds to our literature supporting safety of transarterial chemoembolization for colorectal metstatic disease, many questions still remain. There is still no clear position for transarterial chemoembolization nor transarterial radioembolization in the armamentarium for treatment of mestastatic colorectal cancer. Should these be considered third line, fourth line, or salvage therapy? Is radiation or chemoembolic superior? What size embolic is ideal for chemoembolization? Clearly, more research needs to be performed in this realm, especially to compete with systemic chemotherapy trials and seemingly endless supply of novel chemotherapeutics emerging on the market.
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Fereydooni A, Letzen B, Ghani M, et al. Irinotecan-Eluting 75-150-µm Embolics Lobar Chemoembolization in Patients with Colorectal Cancer Liver Metastases: A Prospective Single-Center Phase I Study. J Vasc Interv Radiol. 2018. Oct 15.
David M Mauro, MD
Department of Radiology
Vascular and Interventional Radiology
University of North Carolina