Chemoembolisation of Non Resectable, Non Metastatic Hepatocellular Carcinomas

Chemoembolisation of Non Resectable, Non Metastatic Hepatocellular Carcinomas Combining DC Bead Microspheres Loaded With Idarubicin (Zavedos®): Phase I Trial

The purpose of this study is to determine the maximal tolerated dose of idarubicin for chemoembolization of non resectable non metastatic hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related death worldwide. Most of the patients are diagnosed at intermediate-advanced stage when the sole standard treatment is transarterial chemoembolization (TACE). In the literature, survival rates in TACE studies vary widely and finally, there is no suggestion for the best chemotherapeutic agent or the optimal treatment regimen.

We hypothesise that the use of idarubicin (the most cytotoxic drug on HCC cell lines) in DC Bead would enhance the efficacy of TACE. The primary objective of the study is to determine the maximal tolerated dose of idarubicin in DC Bead for chemoembolization of non resectable non metastatic hepatocellular carcinoma.

Inclusion Criteria:

• Hepatocellular carcinoma cytologically or histologically proved or diagnosed according the criteria of the American Association for the Study of Liver Diseases(AASLD 2005)
• Three nodules maximum (unilobar disease without limitation in the number of nodules; 3 maximum nodules if bilobar disease [satellite nodules <1cm not included in the total sum])
• Child-Pugh score A or B7
• ECOG Performance Status < 2
• Platelet count > 50,000/µl and absolute neutrophil count (ANC) >1,000/µl
• Serum creatinine < 150 µmol/l
• Resting ejection fraction > 50% (echocardiography or isotopic method)
• Age > 18 years
• Signed written informed consent

Exclusion Criteria:

• Patients eligible for surgical resection or hepatic transplantation or radiofrequency ablation
• Extrahepatic metastases
• Known gastrointestinal bleeding up to 30 days before study entry
• Patients with anticoagulant treatment
• Evidence of portal vein thrombosis
• Pregnancy
• Clinically serious infection
• Known hypersensitivity to anthracyclines
• Known hypersensitivity to contrast medium