Abstract

DTIC was first introduced to Japan in 1977, and DAV combination chemotherapy using DTIC, ACNU and VCR became widely used to treat malignant melanoma. Used especially as a postoperative adjuvant chemotherapy, improvement in survival rates has been reported in multicenter research. Meanwhile, clinical trials commencing in 1978 of natural IFN-β produced from human fibroblasts demonstrated an efficacy rate of 50% for cutaneous metastasis of malignant melanoma, and Feron® was subsequently approved, in 1985. It has also been shown that Feron has an antineo-plastic effect: after subcutaneous administration at the site of melanoma in malignant melanoma patients. Feron levels taper gradually, but still remain in the local region 24hours later, while the drug is transported to regional lymph nodes in high concentrations. A concomitant effect for DAV+IFN-β was investigated in basic experiments, in which additive suppression of tumor proliferation was observed.
With a view to further improving prognosis, therefore, we developed a protocol for Feron plus DAV combination therapy, in which DAV as postoperative adjuvant therapy would be provided in combination with the local administration of Feron, commencing a trial in centers across Japan in 1988. By 1995, 957 cases at 67 centers nationwide had been registered, the results tabulated and prognoses examined. Excellent results were obtained for 5-year suvival rate, classified by Stage, as follows: 98.0% for Stage I, 85.4% for Stage II, 65.8% for Stage III, and 35.0% for Stage IV. These results suggest that prognosis of malignant melanoma is better improved by DAV Feron therapy than by DAV therapy alone, and that combination therapy using Feron and DAV is therefore preferable.