Effects of the mTOR inhibitor sirolimus in patients with hepatocellular and cholangiocellular cancer.

• BACKGROUND: Hepatocellular cancer (HCC), as well as cholangiocellular cancer (CCC), has an extremely poor prognosis due to the extent of tumor at diagnosis and the underlying liver disease. Sirolimus is used in the transplantation setting as an immunosuppressive agent, but it also possesses antiproliferative and antiangiogenic properties. The objective of the study was to evaluate the effect of sirolimus on HCC and CCC. METHODS: In a prospective single-arm protocol, the tumor response to sirolimus as the primary endpoint was studied in 21 patients with advanced HCC and nine with CCC. Sirolimus was administered once daily by mouth, with the dose adjusted to a serum trough level between 4 and 15 mug/ml. Tumor response was evaluated by computed tomography (CT) or magnetic resonance imaging (MRI), according to the Response Evaluation Criteria in Solid Tumors (RECIST), every third month. Secondary measures were overall survival, time to tumor progression, tumor markers, and side effects. RESULTS: Of the patients with HCC, one had partial remission (PR) and fi ve patients had stable disease (SD) at 3 months. Of the patients with CCC, three had SD. The median survival for patients with HCC was 6.5 months (range, 0.2-36 months) and that for patients with CCC was 7 months (range, 2.6-35 months). CONCLUSION: Treatment of HCC and CCC with sirolimus can induce temporary PD or SD. This pilot study indicates that sirolimus might be a promising drug for this treatment, but further clinical studies elucidating the biological effects are advocated.

Nyckelord

1-Phosphatidylinositol 3-Kinase

antagonists & inhibitors

Adult

Aged

Antibiotics

Antineoplastic

therapeutic use

Bile Duct Neoplasms

diagnosis

drug therapy

mortality

Bile Ducts

Intrahepatic

Carcinoma

Hepatocellular

diagnosis

drug therapy

mortality

Cholangiocarcinoma

diagnosis

drug therapy

mortality

Female

Humans

Liver Neoplasms

diagnosis

drug therapy

mortality

Male

Middle Aged

Protein Kinases

metabolism

Sirolimus

therapeutic use

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