IMMUNOTHERAPY WITH LOW-DOSE INTERLEUKIN-2 IN ASSOCIATION WITH MELATONIN AS SALVAGE THERAPY FOR METASTATIC SOFT-TISSUE SARCOMAS

Polychemotherapy represents the only standard medical therapy of metas tatic soft tissue sarcomas (STS), whereas the recent biotherapies with cytokines, such as interleukin-2 (IL-2), seem not to have a relevant therapeutic role. The pineal hormone melatonin (MLT), whose immunomodu lating activity is well known, would seem to exert a direct cytostatic action on STS cell proliferation. Moreover, MLT has been proven to am plify IL-2 efficacy. On this basis, a pilot phase II study with low-do se IL-2 plus MLT has been performed in untreatable metastatic STS pati ents. The study included 13 evaluable metastatic STS patients with poo r PS, who progressed on at least one previous polychemotherapeutic lin e. IL-2 was injected subcutaneously at 3 million IU/day for 6 days/wee k for 4 weeks and MLT was given orally at 40 mg/day in the evening. A partial response was achieved in one patient with leiomyosarcoma. Eigh t other patients had a stable disease (SD) whereas the remaining 4 pat ients progressed. A survival longer than 1 year was achieved in 6/13 p atients and the percent of 1-year survival was significantly higher in patients with response or SD than in the progressed ones (6/9 vs 0/4) . Mean increases in lymphocyte and eosinophil numbers were significant ly higher in patients with response or SD than in the progressed ones. These preliminary results would suggest that immunotherapy with low-d ose IL-2 plus MLT may have some impact at least on the survival time o f untreatable metastatic STS patients with poor clinical conditions.