Context:No efficacious treatments are to date available for advanced medullary thyroid carcinoma (MTC).Objective:We investigated in vitro and in vivo a new strategy for the therapy of MTC, combining human recombinant interleukin 2 (IL-2) with lanreotide (LAN), a somatostatin analog.Methods:The in vitro effects of LAN on the sensitivity of TT cells, a MTC cell line, to IL-2-stimulated human peripheral blood mononuclear cells (PBMC) have been determined by lactate-dehydrogenase (LDH)-release assay. In addition, we evaluated the toxicity, the effects on quality of life (QoL) and the antitumor activity of subcutaneous low dose IL-2 in combination with LAN (90 mg every 28 days) in a series of six patients with symptomatic and advanced MTC.Results:The cytotoxicity of IL-2-activated PBMC was significantly increased in TT cells treated with LAN or LAN plus IL-2, compared to TT cells without treatment. The therapy was well tolerated and a statistically significant improvement of the QoL was observed in patients treated with the combination of LAN and IL-2. After 6 months of therapy, partial response and stable disease have been recorded in two and three patients, respectively, with a significant decrease in calcitonin levels in three cases.Conclusions:Several in vitro and in vivo evidences suggest that the combination of LAN and IL-2 may have a role in the management of advanced and symptomatic MTC. However, these preliminary data require further validation in larger randomized trials.