Long-term Clinical Outcome of Phase IIb Clinical Trial of Percutaneous Injection with Holmium-166/Chitosan Complex (Milican) for the Treatment of Small Hepatocellular Carcinoma

Abstract

Purpose:The purpose of this study was to evaluate the long-term tumor response after phase IIb clinical study and the safety of percutaneous holmium-166 ( 166 Ho)/chitosan complex injection (PHI) therapy for small hepatocellular carcinoma as a local ablative treatment. 166Ho is a radioactive isotope derived from natural holmium-165.We developed a 166 Ho/chitosan complex (Milican, Dong Wha Pharmaceutical Co., Seoul, Korea) using chitosan as a vehicle to retain the radioactive material within the tumor.Experimental Design: Forty patients with single hepatocellular carcinoma <3 cm in maximal diameter were enrolled in this study. The patients either had refused surgery or were poor surgical candidates and were treated with only single session of PHI. Results: Two months after PHI, complete tumor necrosis was achieved in 31 of 40 patients (77.5%) with hepatocellular carcinoma lesions <3 cm and in 11of 12 patients (91.7%) with hepatocellular carcinoma <2 cm. Tumors recurred in 28 patients during the long-term follow-up period, of which 24 recurred at another intrahepatic site.The1-year and 2-year cumulative local recurrence rates were 18.5% and 34.9%, respectively. The survival rates at 1, 2, and 3 years were 87.2%, 71.8%, and 65.3%, respectively. Transient bone marrow depression was serious adverse event requiring hospitalization in two patients. Conclusions: PHI was found to be a safe and novel local ablative procedure for the treatment of small hepatocellular carcinoma and could be used as a bridge to transplantation. A phase III randomized active control trial is clearly warranted among a larger study population.

Combined percutaneous ethanol injection and mitoxantrone versus radiofrequency ablation in the treatment of hepatocellular carcinoma

“…Regional interventional therapies have led to a major breakthrough in the management of unresectable HCC [3]. Furthermore, experiences in interventional radiology, radiation oncology and surgery fields have grown, and new therapeutic choices have been developed including percutaneous ablation therapy, transarterial chemoembolization (TACE), radiation therapy and molecular target therapy [4]. Ablation of the liver tumors is currently the main alternative to formal liver resection.…”

Neutron-Activatable Holmium-Containing Mesoporous Silica Nanoparticles as a Potential Radionuclide Therapeutic Agent for Ovarian Cancer

“…The high density of these microparticles (3.2 g/cm 3 ), which on occasion resulted in particle settling after intracatheter administration, and the lack of photon emissions by 90 Y, which prevented quantitative imaging, led to the development of other neutron-activatable materials. Microparticles composed of lower-density polymers, including polylactic acid (5-7), alginate (8), and chitosan (9) containing 166 Ho, as well as nanosized carrier materials containing stable 165 Ho for subsequent neutron activation to 166 Ho (10)(11)(12), have also been reported. 166 Ho is an attractive radionuclide for radiotherapeutic applications.…”

Synthesis of Highly-loaded Holmium-165 Siloxane Particles for Brachytherapy of Brain Cancer and Injectability Evaluation in Healthy Pig

“…Other types of microparticles composed of lowerdensity polymers, including alginate [11] and chitosan [12] containing 166 Ho, as well as nanosized carrier materials containing stable 165 Ho for subsequent neutron activation [13], have also been reported. However, most of these polymeric carrier materials cannot withstand long neutron irradiation times without degrading or aggregating.…”