IMMUNOTHERAPY WITH LOW-DOSE SUBCUTANEOUS INTERLEUKIN-2 PLUS INTERFERON-BETA AS A 2ND-LINE THERAPY FOR METASTATIC COLORECTAL-CARCINOMA

Aims and Background: Beta-interferon (beta-IFN) has been proven to inf luence some IL-2-induced immune effects. On the basis of these experim ental data, we evaluated the immunobiologic effects of an association between very low-dose IL-2 and R IFN in advanced cancer patients. Meth ods: The study was performed in 15 metastatic colon cancer patients, w ho progressed in response to a first-line chemotherapy with 5-FU plus folates. IL-2 was given subcutaneously at a daily dose of 3 million IU in the evening for 6 days/week for 4 weeks. beta-IFN was injected sub cutaneously at a dose of 3 million U/day for 7 days before the first I L-2 injection, then thrice/week until the end of IL-2 administration. In nonprogressed patients, a second cycle was given after a 14-day res t period. Results: No objective tumor regression was seen. Stable dise ase was obtained only in 2/15 patients; the other 13 progressed. Toxic ity was low in all cases. Natural killer cell and T-activated lymphocy te mean number significantly increased during the immunotherapy. Lymph ocyte and eosinophil mean number also increased, without, however, sig nificant differences. IL-2-induced suppressive events, consisting of a n increase in T-suppressor cell number, and soluble IL-2 receptor leve ls were not blocked by beta-IFN. Conclusions: The study showed that th e concomitant administration of B-IFN may determine an improvement in the immune performance in metastatic cancer patients treated with very low-dose IL-2, even though this biologic improvement does not seem to be associated to a control of tumor development. Further studies in p atients with less advanced disease are needed to better define the imp act of the immune improvement induced by low-dose IL-2 plus beta-IFN o n the clinical course of the neoplastic disease.