title: Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence.
abstract: OBJECTIVE
  To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.
  
  
  METHODS
  A total of 143 patients (83.1% of the 172 participants in the phase II study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase II trial. Safety parameters and the following efficacy endpoints were investigated: (1) time to recurrence; (2) disease-free survival; and (3) overall survival.
  
  
  RESULTS
  PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group: (1) the recurrence-free rate increased from 50% to 63%, and (2) time to recurrence at the 36th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate (11 out of 54 patients). Additionally, subgroup analyses of patients with (1) multiple tumors or a single tumor ≥ 2 cm; and (2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage (56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence.
  
  
  CONCLUSIONS
  Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Juliana
authors.initials: J
authors.lastname: Chang
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Deng-Yn
authors.initials: DY
authors.lastname: Lin
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Long-Bin
authors.initials: LB
authors.lastname: Jeng
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Yih-Jyh
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: King-Tong
authors.initials: KT
authors.lastname: Mok
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Lee
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Hong-Zen
authors.initials: HZ
authors.lastname: Yeh
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Ho
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Sheng-Shun
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Mei-Due
authors.initials: MD
authors.lastname: Yang
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Ming-Chin
authors.initials: MC
authors.lastname: Yu
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Rey-Heng
authors.initials: RH
authors.lastname: Hu
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Kuan-Lang
authors.initials: KL
authors.lastname: Lai
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Stanley Shi-Chung
authors.initials: SS
authors.lastname: Chang
authors.affiliation: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Ming-Chih Ho, Rey-Heng Hu, Pei-Jer Chen, Graduate Institute of Clinical Medicine, Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 10002, Taiwan.
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D009844:Oligosaccharides / Q000008:administration & dosage; D012307:Risk Factors; D016019:Survival Analysis; D013624:Taiwan; D013997:Time Factors; D016896:Treatment Outcome; D000099175:Heparanase
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005966:Glucuronidase; D009844:Oligosaccharides; D000099175:Heparanase; C120158:phosphomannopentaose sulfate
keywords: Adjuvant therapy; Antiangiogenesis; Antimetastasis; Disease-free survival; Heparanase inhibitor; Hepatocellular carcinoma; PI-88; Tumor recurrence