14106 Background: Due to extent of tumour and underlying liver disease primary liver cancer, hepatocellular(HCC) as well as cholangiocellular(CCC), has extremely poor prognosis. The tyrosinekinase and mTOR inhibitor sirolimus, is registered for preventing allograft rejection. It retard experimental liver tumours in rats, and has antiangiogenic effects as well. Methods: Patients with a nonoperable HCC or CCC, with a Karnofsky >70, and the diagnosis confirmed by biopsy or alfa-fetoprotein (>700ug/ml) were eligible. Ethic committee approved the study and informed consent was signed. The daily Sirolimus dose was adjusted to a 6–10 μg/L through-concentration.Twenty patients were to be enrolled in a nonrandomized study. The primary endpoint was to detect a radiological tumor response rate, defined by RECIST criteria, and secondary endpoint was to study the safety profile. CT or MRI were repeated every third month. The study was approved by the Etic Committee of Göteborg University. Results: Eleven patients with HCC and nine with CCC were included. Overall respone rate was 5%, which ocurred in a patient patient with HCC. The PR lasted for 15 months (RR 9% for HCC). Four patients with HCC had SD for median 7 months (range 5–18). Of the patients with CCC four had SD. Median duration of SD was 4 months (range 1 - 7). Median survival for patients with HCC was 7 months (range 2–20) and CCC 4 months (range 2–24) Discussion: There is low evidence supporting the use of chemotherapy for primary liver cancer. For HCC, one PR and 4 SD in this pilot study indicate that sirolimus might be of interest to study in a phase II trial, since the toxicity of sirolimus was low. In the european SILVER study,the impact of sirolimus for patients transplanted for HCC will be clarified. Experimentally, the antiangiogenetic effects of sirolimus has been boosted by combining with 5-FU and gemcitabine. This might translate to impoved response rate also for liver cancer. Conclusions: This pilot study suggests that sirolimus have a tumour effect in patients with HCC. No significant financial relationships to disclose.
