Clinical role of determination of plasma mitotane and its metabolites levels in patients with adrenal cancer: results of a long-term follow-up.

ABSTRACT

Our study aimed at evaluation of the relations between the plasma levels of mitotane (o,p'-DDD) and its metabolites, o,p'-DDA and o,p'-DDE, and the efficacy of Mitotane therapy during a long-term follow-up. Eighteen patients, aged 11 to 70 years, were included to the study. Metastatic or regional stage was diagnosed in 15 patients, while localized disease in three patients. Mitotane has been administered in daily doses of 3.0 to 10.0 g in metastatic and regional stages, and 1.5 to 4.0 g in the localized disease, simultaneously with hydrocortisone, prednisolone and fludrocortisone. Mitotane and its metabolites were determined by a high-pressure liquid chromatographic method. The plasma o,p'-DDD level exceeding 44 _M/L, considered as curative one, was reached in nine cases. The o,p'-DDA/o,p'-DDD ratio rose significantly mainly in the first 1-3 months of therapy. The o,p'-DDE levels rose slowly, reaching higher values in long-term therapy, over 12 months of mitotane administration. In the group of patients with regional or metastatic stage, both the o,p'-DDE levels and the o,p'-DDE/o,p'-DDD ratios were higher in the survivors than in non-survivors. The results of our study suggest that the plasma concentrations of o,p'-DDE were more closely related to clinical improvement or remission than the o,p'-DDD levels.