EFFICACY AND TOLERABILITY OF CANCER NEUROIMMUNOTHERAPY WITH SUBCUTANEOUS LOW-DOSE INTERLEUKIN-2 AND THE PINEAL HORMONE MELATONIN - A PROGRESS REPORT OF 200 PATIENTS WITH ADVANCED SOLID NEOPLASMS

The recent advances in psychoneuroimmunology have demonstrated the exi stence of a psychoneuroendocrine control of the antitumor immunity. Ou r previous preliminary studies indicated the possibility of amplifying the biological and therapeutic efficacy of IL-2 cancer immunotherapy by immunomodulating neurohormones, mainly the pineal indole melatonin (MLT), in most advanced solid tumors, including those which generally do not respond to IL-2 alone. This study reports on the results obtain ed by low-dose IL-2 plus MLT in 200 patients with advanced solid neopl asms, for whom no other effective standard therapy was available. Non- small cell lung cancer, pancreatic adenocarcinoma, hepatocarcinoma, co lon cancer and gastric cancer were the neoplasms most frequently detec ted in our patients. In addition, all patients had a life expectancy l ess than 6 months. IL-2 was given subcutaneously at 3 million IU/day f or 6 days/week for 4 weeks; MLT was given orally at 40 mg/day. In non- progressing patients, a second cycle was given after a 21-day rest per iod; then, patients underwent a maintenance period consisting of one w eek of therapy every month until progression. A complete response (CR) was achieved in 4 patients (hepatocarcinoma 2; pancreas 1; gastric ca ncer 1), a partial reasponse (PR) was achieved in 36 patients (lung 12 ; liver 6; stomach 4; pancreas 3; colon 3; breast 2; miscellaneous 6). Tumor response rate (CR+PR) was 40/200 (20%) patients. Longer than on e year survival was achieved in 79 (39%) patients. Toxicity was mild i n all patients, and therapy was administered as a home therapy. The pr esent study confirms in a great number of patients the possibility to induce objective tumor regressions in most advanced solid tumor histot ypes by low-dose IL-2 plus MLT. Thus, immunotherapy with IL-2 and MLT may be considered as a new well tolerated and effective therapy of alm ost all advanced solid tumors, including those which do not respond to IL-2 alone or to chemotherapy.