A phase I trial of intermittent high-dose alpha-interferon and dexamethasone in metastatic renal cell carcinoma

Evidence exists that the toxic of alpha-interferon can be ameliorated by co-administration of dexamethasone without compromise of therapeutic efficacy. We therefore conducted a phase I trial to determine the maximum tolerated dose of intermittent interferon when combined with oral dexamethasone.

Thirty patients with metastatic renal cell carcinoma were enrolled. The starting dose of interferon was 20 million IU/m2/day given as a subcutaneous injection days 1 to 4 of each 14 day cycle. Dose levels were escalated at increments of 5 million IU/m2. Dexamethasone 4 mg was administered orally every 6 hours during administration of high-dose interferon. Low-dose maintenance interferon, 3 million IU/m2/day, was administered without dose escalation on days 5 to 14 of each cycle.

The maximum tolerated dose of intermittent high-dose interferon was 40 million IU/m2/day. The dose limiting toxicity was fatigue. EEG abnormalities developed in five patients and neuropsychiatric parameters deteriorated significantly in seventeen.

We conclude that co-administration of dexamethasone improves the tolerance of intermittent high-dose interferon. The results of this trial may be useful in designing high-dose interferon regimens for renal cell carcinoma and other interferon-sensitive diseases.