Phase II Study of Transarterial Holmium-166-Chitosan Complex Treatment in Patients with a Single, Large Hepatocellular Carcinoma

Purpose: Holmium-166 ( 166 Ho) is a neutron-activated radioactive isotope whose effectiveness in hepatocellular carcinoma (HCC) was first reported in a preclinical study in 1991. Chitosan is a polymer of 2-deoxy-2-amino-D-glucose that readily forms a chelate with heavy metals and converts from a solution under acidic conditions into a gel under neutral or basic conditions. We performed a prospective trial of a transarterial administration of a radiopharmaceutical 166 Ho-chitosan complex in patients with single, large HCC. Patients and Methods: The study involved 54 patients who had single HCC (≥3 cm) without a vascular shunt and were either inoperable or refused surgery. The 166 Ho-chitosan complex was administered at a dose of 20 mCi per cm of tumor diameter (capping at 200 mCi) via the artery that directly fed the tumor. Results: The median tumor size was 5.3 cm (range: 3–13 cm). The response rate was 78% (42/54), and 31 patients had a complete response for a median duration of 27 months. The incidence of grade 3 or 4 leukopenia was 18.6%, anemia 7.4%, thrombocytopenia 27.8%, AST/ALT elevation 26%/24%, and total bilirubin elevation 5.6%. There were two treatment-related deaths (3.7%). Subset analysis revealed a substantial difference between the two groups categorized by tumor size (3–5 vs. >5 cm) with respect to response rate (p = 0.004) and overall survival (p = 0.02). Conclusion: We found that transarterial administration of the 166 Ho-chitosan complex was highly effective in the treatment of HCC with acceptable toxicities, especially for patients with tumors of 3–5 cm.