Phase II study of transarterial holmium-166-chitosan complex treatment in patients with a single, large hepatocellular carcinoma.
OBJECTIVE
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.


METHODS
The study involved 54 patients who had single HCC (>or=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).


CONCLUSIONS
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.
Sohn
Joo Hyuk
JH
Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Choi
Hye Jin
HJ
Lee
Jong Tae
JT
Lee
Jong Doo
JD
Kim
Joo Hang
JH
Moon
Young Myung
YM
Park
Kyungsoo
K
Park
Kyung Bae
KB
Kim
Eunhee
E
Yoo
Nae Choon
NC
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000532:radiotherapy*; D048271:Chitosan / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D006695:Holmium / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D008111:Liver Function Tests; D008962:Models, Theoretical; D018579:Patient Selection; D011868:Radioisotopes / Q000627:therapeutic use* / Q000633:toxicity; D011879:Radiotherapy Dosage; D015996:Survival Rate; D055815:Young Adult
D000970:Antineoplastic Agents; D011868:Radioisotopes; D048271:Chitosan; D006695:Holmium