Interferon in the Management of Neuroendocrine GEP-Tumors

Interferon has been known to be an effective antiviral and antitumor agent since the 1960s. However, a large majority of solid tumors did not respond to this kind of treatment. In early 1980s, alpha interferon was introduced in the management of classical midgut carcinoids with promising results. Since then, more than 500 patients have been treated with alpha interferon worldwide and published in the literature. The median dose has been 5 million units 3-5 times per week subcutaneously. The subjective response rate is about 60%, biochemical responses in 44% and tumor responses in 11% of the patients. There are very few randomized control trials at the moment which make survival analysis difficult but in different centers median survivals from start of treatment in malignant midgut carcinoids has been reported to be more than 3 years. The mechanisms of action of alpha interferon are direct effects on the tumor cells by inhibiting the cell proliferation via cell cycle block G1-S phase. Induction of interferon inducable genes, such as p-21, p-27, 2-5-A-synthetase, PKR, IRF-1, IRF-2. All these contribute to reduction of the growth potential of the tumor. Furthermore, alpha interferon exerts an immunomodulatory effect stimulating natural killer cells, macrophages and also presents anti-angiogenetic effects. In the future, long-acting formulations of recombinant alpha interferons will come into clinical use, such as polyethylene glycosylated interferons. It will facilitate the treatment for the patients and also perhaps reduce the side effects, which are sometimes significant during treatment with alpha interferon. It might also be possible to give higher doses of alpha interferon with hopefully improved clinical efficacy.