Levamisole and Interleukin-2 for advanced malignancy

Therapy for cancer patients with biologically active immune modulators is a ttractive but has met with limited clinical success. Interleukin-2 (IL2) st imulates T-cells and natural killer (NK) cells to kill tumor cells and leva misole (LMS) is an immunostimulant which has been shown to increase NK cell s and activated T-cells in patients receiving this adjuvantly along with 5F U for Stage III colon cancer. This study was designed to evaluate whether t reatment with LMS prior to IL2 would provide synergistic activity and impro ve response rates. Four patients with advanced malignancies were treated wi th LMS at 50mg po TID for 3 days followed on day 4 with 600,000 units/kg IL 2 as a single iv bolus. This treatment was repeated weekly until progressio n. Serum soluble IL2 receptor (sIL2R) and interferon-gamma levels were moni tored throughout the treatment course as markers of immune activation. All patients had eventual progression of disease. Toxicity was minimal with Gra de II orthostatic hypotension the major consequence of therapy. The pattern of sIL2R levels in 3/4 patients revealed a steady increase over the severa l weeks of therapy, indicating ongoing immunostimulation (r=0.53, p=0.001). Short-term treatment with LMS, however, resulted in a significant and cons istent decreases in sIL2R levels (2198 U/ml vs. 1969 U/ml, p=0.001) in all patients. In conclusion, LMS/IL2 in the dose and schedule utilized here was not clinically effective. However, LMS reduced sIL2R levels immediately fo llowing a three-day course. This reduction in sIL2R by LMS may improve the possibility of response to IL2 by facilitating a decrease in inhibitory sIL 2R. Combinations of these two agents should continue to be investigated as potential synergistic anti-tumor agents.