Phase I-II Study of Gamma Interferon and 5-Fluorouracil for Patients with Metastatic Renal Cell Carcinoma

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Abstract
We have completed a phase I/II trial to evaluate the toxicity and efficacy of the combination of gamma interferon and 5-fluorouracil in metastatic renal cell carcinoma. Gamma interferon was administered at a weekly dose of 100 μg. 5-fluorouracil was given as a 5 day continuous infusion days 1-5 of each 21 day cycle. In the phase I portion of the trial, the gamma interferon dose was held constant, while the 5-fluorouracil was escalated from 500 to 800 mg/m2/day. Serum neopterin and β2 microglobulin were measured prior to and 48 hours after each dose of gamma interferon for the first six weeks of treatment. Dose limiting toxicity was not encountered in the phase I part of the trial; therefore the phase II study was initiated at the 800 mg/m2/day dose of 5-fluorouracil. No responses were seen among 34 patients treated on the phase II trial. Forty-six percent of patients experienced disease stabilization and the remainder progressed through treatment. In the phase I trial, increments in neopterin and β2 microglobulin levels differed significantly between patients treated with lower and higher doses of 5-fluorouracil. We conclude that the addition of 5-fluorouracil to gamma interferon does not appear to enhance the cytokines clinical activity. Incremental increases in macrophage activation markers with escalating 5-fluorouracil doses suggests a role for 5-fluorouracil beyond its usual proposed cytotoxic activity and warrants further investigation into potential immunologic effects of this drug.