A PHASE I II STUDY OF ALTERNATING CONSTANT RATE INFUSION FLOXURIDINE WITH CONSTANT RATE INFUSION VINBLASTINE FOR THE TREATMENT OF METASTATIC RENAL-CELL CARCINOMA/

Background. Metastatic renal cell carcinoma (RCC) is largely chemoresi stant. The efficacy of cell cycle specific chemotherapeutic agents, pa rticularly those with short half-lives, may be enhanced by the use of constant rate infusion schedules. Infusional floxuridine has been demo nstrated to have a response rate of approximately 20%. Infusional vinb lastine has not been tested extensively in patients with metastatic RC C. The sequential use of these agents was designed to increase efficac y and limit toxicity. Methods. Fifteen patients with metastatic RCC we re treated with constant rate infusion floxuridine, 0.075 mg/ kg/day f or 14 days, followed by a constant rate infusion of vinblastine, 0.7 m g/m(2)/day for 14 days. The cycle repeated every 28 days and floxuridi ne and vinblastine doses were incrementally increased until the maximu m tolerated dose (MTD) for each patient was reached. Results. Four pat ients had partial responses (27%), which were maintained for 3, 9, 16 and 19+ months, whereas five patients had stable disease for 3-15 mont hs. Median survival from initiation of therapy was 379 days. Three of four responses occurred in nonpulmonary locations, and all responses o ccurred in patients who had a prior nephrectomy. MTD for floxuridine w as 0.1 mg/kg/ day and for vinblastine, 0.7 mg/m(2)/day. Toxic reaction to floxuridine was limited to diarrhea, whereas the principle dose-li miting toxic reaction for vinblastine was neutropenia. Catheter-relate d complications were also observed. Conclusions. Alternating constant rate infusion floxuridine and constant rate infusion vinblastine is ac tive in the treatment of metastatic RCC. Whether this regimen is super ior to infusional floxuridine is undetermined. Although the toxicity a ssociated with this regimen is manageable, it appears to be more sever e than that reported with infusional floxuridine alone.