INTERFERON-ALPHA-2B PLUS FLOXURIDINE IN METASTATIC RENAL-CELL CARCINOMA - A PHASE-I-II STUDY

Background. Both alpha-interferon and floxuridine are active in metast atic renal cell carcinoma (MRCC); the two agents have demonstrated ant itumor synergism and different clinical toxicities. The purpose of thi s study was to determine the maximum tolerable dose (MTD) of floxuridi ne (FUDR), administered as a constant continuous infusion for 14 days every 28 days, in combination with fixed doses of alpha-2B-interferon and to preliminarily evaluate the antitumor activity of this combinati on. Methods. Sixteen patients entered the study; six had previously re ceived alpha-interferon. Alpha-2B-interferon was administered at the d ose of 10 x 10(6) IU intramuscularly 3 times/week and floxuridine at t he starting daily dose of 0.075 mg/kg. This dose was escalated at each subsequent cycle up to dose-limiting toxicity. Results. Most common t oxicities included fever and flue-like symptoms, fatigue, anorexia, di arrhea, mucositis, and nausea, and 55% of patients experienced greater than or equal to Grade 2 toxicity, mostly diarrhea, for floxuridine d oses greater than 0.125 mg/kg/d. Among 15 evaluable patients, 1 achiev ed a complete response and 4 achieved a partial one (33%; 95% confiden ce interval, 12-62%). Three partial responses were obtained in patient s pretreated with alpha-interferon plus vinblastine. Conclusions. The combination of alpha-2B-interferon and floxuridine is feasible, and in our regimen the recommended daily dose of floxuridine for Phase II st udies was 0.125 mg/kg. This combination is active in metastatic renal carcinoma, but further studies are needed to determine whether alpha-2 B-interferon has added anything to the FUDR infusion or vice versa.