AIMS AND BACKGROUND: Patients with disseminated gastric cancer are generally in very bad clinical conditions, which make them not eligible for potentially active polychemotherapies. This justifies the development of less toxic therapies such as the use of biological response modifiers. 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 activity, which becomes biologically effective also at very low doses. Based on these considerations, a pilot study was performed with low-dose subcutaneous IL-2 in combination with MLT in metastatic gastric cancer patients with low performance status. METHODS: The study included 14 patients 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 starting 7 days before IL-2. In patients in whom the disease did not progress, a second cycle was given after a rest period of 21 days. RESULTS: A tumor regression was obtained in 3/14 (21%) patients, complete response in 1 and partial in 2, with a median duration of 13 + months. The disease stabilized in 6/14 (43%) patients and progressed in the remaining 5 (36%). Survival was significantly longer in patients with response or stable disease than in those with progression. Toxicity was low in all cases. CONCLUSIONS: These preliminary results show that the combination on of low-dose subcutaneous IL-2 and the pineal hormone MLT may represent a new well tolerated biotherapy, capable of inducing objective tumor regression also in patients with metastatic gastric cancer and low performance status.
AIMS AND BACKGROUND: Patients with disseminated gastric cancer are generally in very bad clinical conditions, which make them not eligible for potentially active polychemotherapies. This justifies the development of less toxic therapies such as the use of biological response modifiers. 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 activity, which becomes biologically effective also at very low doses. Based on these considerations, a pilot study was performed with low-dose subcutaneous IL-2 in combination with MLT in metastatic gastric cancer patients with low performance status. METHODS: The study included 14 patients 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 starting 7 days before IL-2. In patients in whom the disease did not progress, a second cycle was given after a rest period of 21 days. RESULTS: A tumor regression was obtained in 3/14 (21%) patients, complete response in 1 and partial in 2, with a median duration of 13 + months. The disease stabilized in 6/14 (43%) patients and progressed in the remaining 5 (36%). Survival was significantly longer in patients with response or stable disease than in those with progression. Toxicity was low in all cases. CONCLUSIONS: These preliminary results show that the combination on of low-dose subcutaneous IL-2 and the pineal hormone MLT may represent a new well tolerated biotherapy, capable of inducing objective tumor regression also in patients with metastatic gastric cancer and low performance status.