Alpha-2B-interferon plus floxuridine in metastatic renal cell carcinoma: A phase I-II study

Background. Both alpha-interferon and floxuridine are active in metastatic renal cell carcinoma (MRCC); the two agents have demonstrated antitumor synergism and different clinical toxicities. The purpose of this study was to determine the maximum tolerable dose (MTD) of floxuridine (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 combination. Methods. Sixteen patients entered the study; six had previously received alpha-interferon. Alpha-2B-interferon was administered at the dose of 10 x 10⁶ IU intramuscularly 3 times/week and floxuridine at the starting daily dose of 0.075 mg/kg. This dose was escalated at each subsequent cycle up to dose- limiting toxicity. Results. Most common toxicities included fever and flue- like symptoms, fatigue, anorexia, diarrhea, mucositis, and nausea, and 55% of patients experienced greater than or equal to Grade 2 toxicity, mostly diarrhea, for floxuridine doses greater than 0.125 mg/kg/d. Among 15 evaluable patients, 1 achieved a complete response and 4 achieved a partial one (33%; 95% confidence interval, 12-62%). Three partial responses were obtained in patients 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 studies was 0.125 mg/kg. This combination is active in metastatic renal carcinoma, but further studies are needed to determine whether alpha- 2B-interferon has added anything to the FUDR infusion or vice versa.