In vitro demonstration of synergy/additivity between (188)rhenium and sorafenib on hepatoma lines: preliminary results.

Background: Hepatocellular carcinoma is generally diagnosed at advanced stages, for which only palliative treatments are possible by intra-arterial route or by targeted therapies. Among these treatments, metabolic radiotherapy using (90)-yttrium or Re-188 and sorafenib are two options adopted in monotherapy. Materials and Methods: We address the question of a possible synergy arising from the combination of these two treatments. Two primary malignant hepatoma cell lines, N1S1 (murine HCC) and HepG2 (human hepatoblastoma) were treated in media containing increasing concentrations of sorafenib with/without Re-188 to assess the cellular toxicities of each treatment alone and in combination. The combination index method was used to look for synergy or additivity. Results: A synergistic advantage of a treatment combining Re-188 and sorafenib is shown in vitro on hepatoma cell lines. Conclusion: This combined approach is promising and now needs to be confirmed by more complex in vitro models integrating the tumoral stroma, as well as by in vivo studies.