o,p′-DDD (mitotane) therapy of adrenal cortical carcinoma. Observations on drug dosage, toxicity, and steroid replacement

Abstract

Four patients with adrenal cortical carcinoma were treated with standard doses of o,p'-DDD. Plasma levels of o,p'-DDD and its metabolites o,p'-DDA and o,p'-DDE were measured. o,p'-DDD was measurable for up to 8 months after stopping therapy, and trace levels of metabolites were detectable at 18 months. Although 2 of 3 patients with measurable disease had objective tumor response and one patient achieved a complete response, severe drug toxicity occurred in all patients and signs of adrenal insufficiency occurred in three. Low dose therapy with o,p'-DDD is suggested, together with full gluco and mineralocorticoid replacement. Measurement of o,p'-DDD and its metabolites in plasma may prove clinically useful in developing effective but less toxic dosage schedules.

Mitotane reduces human and mouse ACTH-secreting pituitary cell viability and function

“…Recently, a retrospective study has highlighted the efficacy of mitotane therapy in CD treatment (Baudry et al 2012). Mitotane (o,p 0 -DDD), a derivative of the insecticide dichlorodiphenyltrichloroethane, has been widely used for treatment of advanced (unresectable, metastatic, or relapsed) adrenocortical carcinoma (ACC; Bergenstal et al 1960, Young et al 1973, Hogan et al 1978, Lughezzani et al 2010 and is increasingly used in adjuvant settings (Fassnacht et al 2012). Mitotane concentrations are associated with both efficacy and toxicity (Haak et al 1994, Terzolo et al 2000 and blood levels R14 mg/l predict ACC tumor response (Haak et al 1994, Hermsen et al 2011.…”

Successful Treatment of a Metastatic Hormone-Producing Adrenal Cancer by a Combination of Mitotane, Tegafur and Surgical Resection.

“…The endocrine data (Moolenaar et al, 1975;Hogan et al, 1978;Slooten et al, 1984). in predicting the tumor response to M, but also useful in predicting the occurrence of adverse effects of CNS toxicities due to the drug, as already reported .…”

“…No standard has been established for treat-ment, and the overall prognosis has usually been poor. Mitotane (M) has been widely employed as the most promising adjuvant therapy (Hutter and Kayhoe 1966;Hoffman and Mattox 1972;Lubitz et al, 1973), and a few isolated cases demonstrated dramatic response to the drug (Dowing et al, 1974;Ostuni and Roginsky et al, 1975;Jabarak and Rice et al, 1981;Boven et al, 1984;Slooten et al 1984;Naruse et al, 1984;Hogan et al, 1978). Evaluation of the serum and subcutaneous M concentrations as a guide to M therapy have been tried (Moolenaar and von Seters 1975;Slooten et al, 1982Slooten et al, , 1984Hogan et al, 1978), but results are controversial.…”

Maligne Tumoren der Nebennierenrinde

“…Häufiger gelingt eine Beeinflussung der pathologischen Hormonproduktion (30-70%). Eine Tumorregression wurde in unterschiedlichen Studien in einem Prozentsatz von 15-60% beobachtet [11,13,21,22,23,24,25,26,27,28,29,30]. Langsam wachsende Karzinome mit endokriner Aktivität sprechen offenbar eher an als rasch progrediente, undifferenzierte endokrin inaktive Tumoren.…”