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Background/Aims: PI-88 is a first in class mimetic of heparan sulfate (HS) which targets two biological processes critical to the growth and progression of solid tumours: angiogenesis and metastasis. It antagonises HS interaction with angiogenic growth factors and inhibits cleavage of HS by heparanase in the extracellular matrix. Approximately 17,500 doses of PI-88 have been administered to 427 subjects at a variety of dosing regimens in phase I and phase II clinical trials in multiple myeloma, hepatocellular carcinoma (HCC), lung cancer, metastatic melanoma and prostate cancer. Overall, PI-88 has been well tolerated with an acceptable safety profile and has shown early signs of benefit in patients. Despite high first-year recurrence rates, few treatment options exist for patients in the adjuvant HCC setting. This phase II trial represents a unique opportunity to assess anti-angiogenic compounds, such as PI-88, in a patient population with a low tumour burden and aims to evaluate the efficacy and safety of PI-88 in patients with HCC following curative hepatic resection.

Methods: The trial was a randomized, three-arm, open label study. Following curative HCC resection, eligible patients were randomized 1:1:1 to an untreated control arm, or to self-administer subcutaneously one of two dose levels of PI-88 (160 or 250 mg/day) for 4 consecutive days per week for 3 weeks followed by a 1 week observation period. Patients were treated for up to 9 treatment cycles (36 weeks), with a follow-up period of 12 weeks, to assess disease-free rate and time to first recurrence.

Results: The trial recruited 172 Asian patients at six centres in Taiwan. 169 patients were evaluable for efficacy (median age = 53; M:F = 134:35; HBV:HCV:HBV+HCV:NBNC = 115:29:9:16). 38 patients (22%) had a CLIP score ≥ 3; 39 patients (23%) showed vascular invasion and 95 patients (53%) presented with liver cirrhosis. Preliminary safety data indicates that PI-88 has been well tolerated in this study, particularly at 160 mg/day.

Conclusions: PI-88was well tolerated in this patient population and warrants further investigation. Preliminary disease-free survival and recurrence rates at 30 weeks will be presented.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA