Document Detail

Heparanase inhibitor PI-88 as adjuvant therapy for hepatocellular carcinoma after curative resection: a randomized phase II trial for safety and optimal dosage.
MedLine Citation:
PMID:  19303160     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: Hepatocellular carcinoma recurrence after curative treatment adversely influences clinical outcome. It is important to explore adjuvant therapies. This phase II/stage 1 multi-center, randomized trial investigated the safety, optimal dosage and preliminary efficacy of PI-88, a novel heparanase inhibitor, in the setting of post-operative recurrence of HCC according to a Simon's 2-stage design.
METHODS: Three groups were included: one untreated arm (Group A) and two PI-88 arms (Group B: 160 mg/day; Group C: 250 mg/day). Treatment groups received PI-88 over nine 4-week treatment cycles, followed by a 12-week treatment-free period. Safety and optimal dosage were assessed.
RESULTS: Overall, 172 patients were randomized and 168 were included in the intention-to-treat (ITT) population. Treatment-related adverse effects included cytopenia, injection site hemorrhage, PT prolongation, etc. Four serious adverse events were possibly related to PI-88 treatment. One (1.8%) group B patients and six (10.5%) group C had hepatotoxicity-related withdrawals. Among the ITT population, 29 patients (50%) in Group A, 35 (63%) in Group B, and 22 (41%) in Group C remained recurrence-free at completion. Calculated T(1) value suggested 160 mg/day treatment satisfied the criteria for the next stage of the trial.
CONCLUSIONS: PI-88 at 160 mg/day is optimal and safe, and shows preliminary efficacy as an adjunct therapy for post-operative HCC.
Chun-Jen Liu; Po-Huang Lee; Deng-Yn Lin; Cheng-Chung Wu; Long-Bin Jeng; Pin-Wen Lin; King-Tong Mok; Wei-Chen Lee; Hong-Zen Yeh; Ming-Chih Ho; Sheng-Shun Yang; Ching-Chih Lee; Ming-Chin Yu; Rey-Heng Hu; Cheng-Yuan Peng; Kuan-Lang Lai; Stanley Shi-Chung Chang; Pei-Jer Chen
Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2009-02-15
Journal Detail:
Title:  Journal of hepatology     Volume:  50     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-22     Completed Date:  2009-08-17     Revised Date:  2012-08-24    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  958-68     Citation Subset:  IM    
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, 1 Chang-Te Street, Taipei 10002, Taiwan.
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MeSH Terms
Carcinoma, Hepatocellular / drug therapy*,  surgery*
Chemotherapy, Adjuvant
Combined Modality Therapy
Dose-Response Relationship, Drug
Enzyme Inhibitors / adverse effects,  therapeutic use*
Glucuronidase / antagonists & inhibitors*
Liver Neoplasms / drug therapy*,  surgery*
Middle Aged
Neoplasm Recurrence, Local / prevention & control
Oligosaccharides / adverse effects,  therapeutic use*
Treatment Outcome
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Oligosaccharides; 0/phosphomannopentaose sulfate; EC 3.2.1.-/heparanase; EC
Comment In:
J Hepatol. 2009 May;50(5):850-3   [PMID:  19329214 ]

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