SUBCUTANEOUS THERAPY WITH LOW-DOSE INTERLEUKIN-2 PLUS THE NEUROHORMONE MELATONIN IN METASTATIC GASTRIC-CANCER PATIENTS WITH LOW PERFORMANCESTATUS

Aims and background: Patients with disseminated gastric cancer are gen erally in very bad clinical conditions, which make them not eligible f or potentially active polychemotherapies. This justifies the developme nt of less toxic therapies such as the use of biological response modi fiers. Unfortunately, IL-2, one of the most promising cytokines, does not seem to be effective in gastric cancer. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify IL-2 activit y, which becomes biologically effective also at very low doses. Based on these considerations, a pilot study was performed with low-dose sub cutaneous IL-2 in combination with MLT in metastatic gastric cancer pa tients with low performance status. Methods: The study included 14 pat ients with metastatic gastric cancer who received IL-2 at a dose of 3 million IU/day at 8.00 p.m. subcutaneously for 6 days/week for 4 weeks . MLT was given orally at a dose of 50 mg/day at 8.00 p.m. every day s tarting 7 days before IL-2. In patients in whom the disease did not pr ogress, a second cycle was given after a rest period of 21 days. Resul ts: A tumor regression was obtained in 3/14 (21%) patients, complete r esponse in 1 and partial in 2, with a median duration of 13+ months. T he disease stabilized in 6/14 (43%) patients and progressed in the rem aining 5 (36%). Survival was significantly longer in patients with res ponse or stable disease than in those with progression. Toxicity was l ow in all cases. Conclusions: These preliminary results show that the combination on of low-dose subcutaneous IL-2 and the pineal hormone ML T may represent a new well tolerated biotherapy, capable of inducing o bjective tumor regression also in patients with metastatic gastric can cer and low performance status.