Immunotherapy with low-dose subcutaneous interleukin-2 plus beta-interferon as a second-line therapy for metastatic colorectal carcinoma.

Aims and Background: Beta-interferon (beta-IFN) has been proven to influence some IL-2-induced immune effects. On the basis of these experimental data, we evaluated the immunobiologic effects of an association between very low-dose IL-2 and beta-IFN in advanced cancer patients.
Methods: The study was performed in 15 metastatic colon cancer patients, who 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 subcutaneously at a dose of 3 million U/day for 7 days before the first IL-2 injection, then thrice/week until the end of IL-2 administration. In nonprogressed patients, a second cycle was given after a 14-day rest period.
Results: No objective tumor regression was seen. Stable disease was obtained only in 2/15 patients; the other 13 progressed. Toxicity was low in all cases. Natural killer cell and T-activated lymphocyte mean number significantly increased during the immunotherapy. Lymphocyte and eosinophil mean number also increased, without, however, significant differences. IL-2-induced suppressive events, consisting of an increase in T-suppressor cell number, and soluble IL-2 receptor levels were not blocked by beta-IFN.
Conclusions: The study showed that the concomitant administration of beta-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 patients with less advanced disease are needed to better define the impact of the immune improvement induced by low-dose IL-2 plus beta-IFN on the clinical course of the neoplastic disease.