Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence.

Abstract

AIM:

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.

CONCLUSION:

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: Chun-Jen Liu, Juliana Chang, Po-Huang Lee, Deng-Yn Lin, Cheng-Chung Wu, Long-Bin Jeng, Yih-Jyh Lin, King-Tong Mok, Wei-Chen Lee, Hong-Zen Yeh, Ming-Chih Ho, Sheng-Shun Yang, Mei-Due Yang, Ming-Chin Yu, Rey-Heng Hu, Cheng-Yuan Peng, Kuan-Lang Lai, Stanley Shi-Chung Chang, Pei-Jer Chen
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 20 Issue 32 Pg. 11384-93 (Aug 28 2014) ISSN: 2219-2840 [Electronic] United States
• PMID: 25170226 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Observational Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Oligosaccharides
• phosphomannopentaose sulfate
• heparanase
• Glucuronidase

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage)
• Carcinoma, Hepatocellular (drug therapy, enzymology, mortality, pathology)
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Drug Administration Schedule
• Enzyme Inhibitors (administration & dosage)
• Female
• Glucuronidase (antagonists & inhibitors, metabolism)
• Humans
• Liver Neoplasms (drug therapy, enzymology, mortality, pathology)
• Male
• Middle Aged
• Oligosaccharides (administration & dosage)
• Risk Factors
• Survival Analysis
• Taiwan
• Time Factors
• Treatment Outcome