Normal metyrapone response after 1 month of high-dose methylprednisolone in cancer patients: a phase I study

A dose of 125 mg of methylprednisolone was given iv each morning for 28 days to six patients with cancer. The posttreatment mean AM/PM serum cortisol (hydrocortisone) level of 19.55/11.27 microgram/dl showed a statistically significant (P less than 0.05) diurnal rhythm and did not differ from the pretreatment level (19.28/11.85 microgram/dl). The response to metyrapone (750 mg orally, every 4 hours X six doses) was assessed in five of the six patients before and after treatment. No abnormally low Compound S (11-deoxycortisol) levels were observed. The mean serum Compound S level (15.30 microgram/dl) achieved after treatment did not differ significantly from the pretreatment mean level (20.24 microgram/dl, P greater than 0.1). No adverse clinical effects were observed during or after this steroid treatment. Since significant hypothalamic-pituitary-adrenal suppression has not been demonstrated, this regimen appears to be safe for use in controlled studies of clinical efficacy.