A PHASE-I TRIAL OF INTERMITTENT HIGH-DOSE ALPHA-INTERFERON AND DEXAMETHASONE IN METASTATIC RENAL-CELL CARCINOMA

Background: Evidence exists that the toxic effects of cc-interferon ca n be ameliorated by co-administration of dexamethasone without comprom ise of therapeutic efficacy. We therefore conducted a phase I trial to determine the maximum tolerated dose of intermittent interferon when combined with oral dexamethasone. Patients and methods: Thirty patient s with metastatic renal cell carcinoma were enrolled. The starting dos e of interferon was 20 million IU/m(2)/day given as a subcutaneous inj ection days 1 to 4 of each 14 day cycle. Dose levels were escalated at increments of 5 million IU/m(2). Dexamethasone 4 mg was administered orally every 6 hours during administration of high-dose interferon. Lo w-dose maintenance interferon, 3 million IU/m(2)/day, was administered without dose escalation on days 5 to 14 of each cycle. Results: The m aximum tolerated dose of intermittent high-dose interferon was 40 mill ion IU/m(2)/day. The dose limiting toxicity was fatigue. EEG abnormali ties developed in five patients and neuropsychiatric parameters deteri orated significantly in seventeen. Conclusions: We conclude that co-ad ministration of dexamethasone improves the tolerance of intermittent h igh-dose interferon. The results of this trial may be useful in design ing high-dose interferon regimens for renal cell carcinoma and other i nterferon-sensitive diseases.