Phase I-II study of interferon-gamma and eflornithine (DFMO) in patients with advanced renal cell carcinoma, malignant melanoma and colorectal carcinoma

Eflornithine (DFMO) and interferon-gamma (IFN-gamma) are known to exert synergistic activity on inhibition of ornithinedecarboxylase (ODC) in vitro and in experimental animal tumors thereby inhibiting tumor proliferation. In this study, we prospectively investigated therapeutic effects and side effects of a combination of DFMO and IFN-gamma in 15 patients with renal cell carcinoma (RCC), 9 with malignant melanoma (MM), and 9 with colorectal carcinoma (CRC). DEMO was given orally at a dose of 3x4 g/day during the first 2 weeks of each month; IFN-gamma was administered daily subcutaneously during the DFMO administration periods and every other day during the following 2 weeks. The starting dose of IFN-gamma was 30 mu g/m(2) in the first 5 patients and 60 mu g/m(2) in the next 28. IFN-gamma dose was doubled every 4 weeks to a maximum dose of 120 mu g/m(2) and 240 mu g/m(2), respectively. Therapy was applied for three months in cases with stable disease or partial remission. In 15 patients treatment was stopped after 3 to 11 weeks after initiation of therapy because of tumor progression (14 cases) or severe side effects (1 case). In one out of 15 patients with renal cell carcinoma a partial response was observed lasting 7 months, 5 patients showed stable disease, and 9 progressed. In patients with malignant melanoma and colorectal carcinoma, stable disease was observed in one patient and progressive disease in 8 patients per group. The most frequent side effects were fever and gastrointestinal disturbances observed in 26 patients each. The results of this study indicate that DFMO combined with IFN-gamma has no significant therapeutic activity in patients with advanced renal cell carcinoma, malignant melanoma, and colorectal carcinoma.