Clinical and pharmacologic study of ADI-PEG20 in hepatocellular carcinoma

15584 Background: It has been reported that hepatocellular carcinoma (HCC) possess low levels of argininosuccinate synthetase (ASS), a key enzyme needed to synthesize arginine (Arg) from citrulline. Thus, Arg depletion using pegylated arginine deiminase (ADI-PEG20 from Polaris Inc.) results in tumor cell death. Clinical trials using ADI-PEG20 have shown antitumor activity in HCC (J.Gastro.Hep. 207:86- 91,2007). However, not all HCC lack ASS expression. In addition to a clinical trial of ADI-PEG20 in HCC, we have studied ASS expression in tumor samples. Methods: Eligibility criteria include: advanced, unresectable HCC with KPS>70. Treatment: Patients (pts) were treated with ADI-PEG20 at 160 IU/m2 i.m. weekly. CT/MRI scans were done every 2 months. ASS expression was performed by immunohistochemical staining as well as by real time RT-PCR(RPCR). RRT-PCR was performed using a set of ASS primer and GADPH primer which have similar efficiency of amplification. The ratio of GADPH and ASS was calculated. Normal h...