IMMUNOTHERAPY WITH SUBCUTANEOUS LOW-DOSE INTERLEUKIN-2 AND THE PINEALINDOLE MELATONIN AS A NEW EFFECTIVE THERAPY IN ADVANCED CANCERS OF THE DIGESTIVE-TRACT

The advanced tumours of the digestive tract are generally less respons ive to conventional chemotherapies. Moreover, preliminary results with IL-2 immunotherapy also seem to show a low efficacy. On the basis of our previous studies suggesting s synergistic action between IL-2 and some neurohormones, such as the pineal indole MLT, a clinical trial wa s performed to investigate the clinical efficacy and tolerability of a n immunotherapy with IL-2 plus MLT in patients with advanced neoplasms of the digestive tract. The study included 35 patients (colorectal ca ncer: 14; gastric cancer: 8; hepatocarcinoma: 6; pancreas adenocarcino ma: 7). Distant organ metastases were present in 31/35 patients. MLT w as given orally at a daily dose of 50 mg at 8.00 p.m., starting 7 days before IL-2, which was given subcutaneously at a dose of 3 million IU /day at 8.00 p.m. for 6 days/week for 4 weeks, corresponding to one cy cle of immunotherapy. In nonprogressed patients, a second cycle was gi ven after a 21-day rest period. A complete response was achieved in tw o patients (gastric cancer: 1; hepatocarcinoma: 1). Six other patients obtained a partial response: (gastric cancer: 2; hepatocarcinoma: 2; colon cancer: 1; pancreas cancer: 1). Therefore, the overall response rate was 8/35 (23%). Stable disease was obtained in 11/35 (31%) patien ts, whereas the remaining 16 patients (46%) progressed. The response r ate was significantly higher in untreated patients than in those previ ously treated with chemotherapy. Toxicity was low in all patients, who received the treatment as a home therapy. This study shows that the i mmunotherapy with low-dose IL-2 plus the pineal hormone MLT is a new w ell tolerated and effective therapy of advanced tumours of the digesti ve tract, mainly in gastric cancer and hepatocarcinoma.