title: Phase II study of transarterial holmium-166-chitosan complex treatment in patients with a single, large hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joo Hyuk
authors.initials: JH
authors.lastname: Sohn
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Jong Tae
authors.initials: JT
authors.lastname: Lee
authors.forename: Jong Doo
authors.initials: JD
authors.lastname: Lee
authors.forename: Joo Hang
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Myung
authors.initials: YM
authors.lastname: Moon
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Park
authors.forename: Kyung Bae
authors.initials: KB
authors.lastname: Park
authors.forename: Eunhee
authors.initials: E
authors.lastname: Kim
authors.forename: Nae Choon
authors.initials: NC
authors.lastname: Yoo
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D011868:Radioisotopes; D048271:Chitosan; D006695:Holmium