PI-88 in Hepatocellular Carcinoma After Hepatectomy

Although early diagnosis and treatment improve survival, hepatocellular carcinoma (HCC) is rarely cured and recurs frequently after regional therapy or transplantation. Hepatic resection can improve 5-year recurrence-free survival by up to 25%. Micrometastases of HCC have been detected by molecular techniques in 88% of patients at the time of surgery, and probably cause postoperative recurrence. Efforts to reduce the risk of recurrence after a curative resection have been tried, including various regimens of adjuvant and neoadjuvant therapy.

In this study , an anti-angiogenic agent, PI-88, is being used as an adjuvant therapy for HCC patients after curative hepatic resection. The efficacy endpoints, including tumour non-recurrence rate, time to first recurrence and 1-year survival rate are being evaluated. Several risk factors associated with tumour recurrence are also being analysed.

Inclusion criteria

• Patients have voluntarily given written informed consent
• Age ≥ 18 years but ≤ 75 years
• Males or females
• Histological diagnosis of hepatocellular carcinoma
• Curative hepatectomy within the past 4-6 weeks
• ECOG performance status of 0 to 2
• Cardiac functional capacity ≤ to class II (New York Heart Association)
• Patients with adequate renal, hepatic, and haematopoietic function as defined by:

• Serum creatinine ≤ 2.0 mg/dL
• Total bilirubin < 2.5 mg/dL
• Neutrophil count > 1.5 x 10^9/L
• ALT < 5 x upper limit of normal (ULN)
• White blood cell (WBC) count ≥ 3 x 10^9/L
• Platelet count ≥ 80 x 10^9/L
• Prothrombin time international normalized ratio (PT-INR) ≤ 1.3 (or PT-INR ≤ 1.4 but PT within normal range)
• Activated partial thromboplastin time (APTT) < ULN

Exclusion criteria

• Patients with history of allergy and/or hypersensitivity to anticoagulants/thrombolytic agents, especially heparin.
• Patients with history of immune mediated thrombocytopenia, thrombotic thrombocytopenic purpura, or other platelet disease
• Patients with previous positive result in a heparin-induced thrombocytopenia (HIT) antibody test.
• Patients with any tumour metastasis.
• Patients with uncontrolled infection or serious infection within the past 4 weeks.
• Patients with myocardial infarction, stroke, or congestive heart failure within the past 3 months.
• Patients with history of inflammatory bowel disease, any other abnormal bleeding tendency, or patients at risk of bleeding due to open wounds or planned surgery.
• Patients with acute or chronic gastrointestinal bleeding within the past 1 year.
• Patients with a history of drug abuse or psychiatric disorder.
• Patients with known HIV infection or AIDS-related illness.
• Patients who received other investigational or anti-neoplastic medication within the past 4 weeks.
• Use of aspirin, aspirin-containing medications, non-steroidal anti-inflammatory drugs (except for COX-2 inhibitors), heparin, low molecular weight heparin, warfarin, anti-platelet drugs, or any other anticoagulant medications 2 weeks prior to or during the study period.
• Women who are pregnant or breast-feeding.
• Women of child-bearing potential who are not using an adequate method of contraception.