CANCER-IMMUNOTHERAPY WITH LOW-DOSE INTERLEUKIN-2 SUBCUTANEOUS ADMINISTRATION - POTENTIAL EFFICACY IN MOST SOLID TUMOR HISTOTYPES BY A CONCOMITANT TREATMENT WITH THE PINEAL HORMONE MELATONIN

The antitumor efficacy of IL-2 is limited to venal cancer and melanoma . Several cytokines have been associated with IL-2 in an attempt to im prove its activity, without, however, any clear benefit. Recent experi mental and clinical studies have suggested the possibility to manipula te the host biological response by immunomodulating neurohormones, suc h as the pineal hormone melatonin (MLT). On the bases of these conside rations we have designed a neuroimmunotherapeutic protocol with low-Ho se IL-2 subcutaneous therapy (3 million IU/day for 6 days/week for 4 w eeks) plus MLT (40 mg/day orally, starting 7 days before IL-2) in adva nced solid neoplasms other than renal cancer and melanoma, which are g enerally resistant to IL-2 alone. The study included 82 patients, 72 o f whom showed distant organ metastases. Tumor histotypes were, as foll ows: non-small cell lung cancer: 19; hepatocarcinoma: 16; colon cancer : 15; gastric cancer: 11; cancer of pancreas: 11; breast cancer: 6; mi scellaneous: 4. Objective tumor regressions were achieved in 17/82 (21 %) patients, consisting of CR in 4 (liver: 2; pancreas: 1; stomach: 1) and PR in 13 (lung: 4; liver: 4;stomach: 2; pancreas: 1; breast: 1; c olon: 1). The median duration of response was 8(+) months. A stabiliza tion of disease was obtained in 30 patients, while the other 35 patien ts progressed. The lack of progression was associated with a significa ntly higher increase in lymphocyte and eosinophil mean number and with a significantly lower increase in neopterin mean levels. The treatmen t was well tolerated in all patients. These results suggest that the n euroimmunotherapy with low-dose IL-2 and MLT may constitute a well tol erated end active treatment of advanced solid neoplasms, also effectiv e in those tumors which are generally nonresponsive to IL-2 alone.