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.
OBJECTIVE
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. (166)Ho 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.


METHODS
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 11 of 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. The 1-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.
Kim
Ja Kyung
JK
Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei Liver Cancer Study Group, Yonsei University College of Medicine, 134 Shinchoin-dong, Seodaemoon-gu, Seoul, Korea 120-752.
Han
Kwang-Hyub
KH
Lee
Jong Tae
JT
Paik
Yong Han
YH
Ahn
Sang Hoon
SH
Lee
Jong Doo
JD
Lee
Kwan Sik
KS
Chon
Chae Yoon
CY
Moon
Young Myoung
YM
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy*; D048271:Chitosan / Q000627:therapeutic use*; D005260:Female; D006695:Holmium / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy; D011868:Radioisotopes / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D011868:Radioisotopes; D048271:Chitosan; D006695:Holmium