THE EFFICACY OF 2',2'-DIFLUORODEOXYCYTIDINE (GEMCITABINE) AND VINBLASTINE COMBINED WITH INTERFERON IN NUDE-MICE XENOGRAFTS OF HUMAN RENAL-CELL CARCINOMA

Recent in vitro experiments indicated strong activity of 2',2'-difluor odeoxycytidine (dFdC, gemoitabine) in human renal cell carcinoma (RCC) cell lines and an increase of efficacy by combined application of int erferon (IFN). In the present study, nude mice with xenografts from AC HN- or SN12C cells were treated by dFdC, dFdC plus IFN-alpha or vinbla stine (VBL) plus IFN-alpha. ACHN-xenografts were significantly more in hibited by dFdC+/-IFN-alpha than by VBL+IFN-alpha. Complete remissions (CR) were only seen by dFdC. An additional treatment with IFN-alpha s hortened the time to commencement of tumor remission and increased CR of ACHN- and SN12C-tumors (40%; 7%) compared to a treatment with dFdC alone (20%; 0). dFdC+IFN-alpha reduced the number of pulmonary metasta ses compared to untreated animals. Survival was significantly prolonge d by dFdC+/IFN-alpha in ACHN-mice and dFdC+IFN-alpha or VBL+IFN-alpha in SN12C mice. In conclusion, experimental data confirm dFdC as a supe rior drug against human RCC compared to VBL. Combined therapy with IFN -alpha increased the efficacy of dFdC in terms of tumor response in im munodeficient nude mice, thus clinical studies are strongly recommende d in patients with metastatic renal cell carcinoma.