Mitotane

Miscellaneous Agents. Those chemotherapeutic agents, which do not fit into any of the classifications discussed, ate Hsted iu Table 7. Mitotane (67), a stmctural isomer of DDT, is used to iaduce chemical adrenalectomies iu patients having adrenal cancer by teduciug host levels of adrenocorticosteroids. 

Adrenolytic Agent Mitotane 11 P-hydroxylase. Inhibits steroidogenesis intermittently 2-6 g/day in 3-4 Gl intolerance (high Used primarily for adrenal... 

Compazine 10 mg PO/IV 30 minutes before each dose of mitotane if needed... 

Mitotane—if well-tolerated, dose may be doubled on day 3 then, from day 5 onwards, may increase dose by 500 mg every 2-3 days until maximum tolerated dose (8-12 grams daily) has been reached glucocorticoid and mineralocorticoid replacement necessary to prevent adrenal insufficiency increased steroid doses may be needed at times of physiologic stress... 

Mitotane (o,p-DDD) -adrenocortical cytotoxin -nausea and vomiting -CNS toxicity—lethargy, vertigo, sedation, dizziness -adrenal insufficiency—must use replacement doses of mineralocorticoids and glucocorticoids -diarrhea -fever -wheezing -flushing... 

Adrenal carcinoma Surgery Mitotane See above See above See above... 

In addition to hormonal dmgs, five other nonsteroids that have a direct relationship to this section are also nsed in cancer chemotherapy. They are aminoglutethimide, flutamide, mitotan, tamoxifen, and leuprolide. 

Mitotane Mitotane, l,l-dichloro-2-(o-chlorophenyl)ethane (30.5.8), is made by alkylating chlorobenzene with l-(2-chlorophenyl)-2,2-dichloroethane (30.5.7) in the presence of sulfuric acid. The necessary l-(2-chlorophenyl)-2,2-dichloroethanol (30.5.7) is in turn made from reacting 2-chlorophenylmagnesinmbromide with dichloroacetic aldehyde [135]. 

Mitotane, a derivative of the insecticide DDT, quickly lowers the level of corticosteroids, and is metabolized in the blood and urine and used on non-operable metastatic prostate carcinomas. Synonyms of this drug are lysodren and others. 

Drugs that may affect spironolactone include ACE inhibitors, salicylates, and food. Drugs that may be affected by spironolactone include anticoagulants, digitalis glycosides, mitotane, digoxin, and potassium preparations. 

Mitotane, or o,p -DDD, is an oral medication used in the treatment of adrenocortical carcinoma. Chemically it is an isomere of DDT. Following its metabolism in the adrenal cortex to a reactive acyl chloride intermediate, mitotane covalently binds to adrenal proteins, specitically inhibiting adrenal cortical hormone production. The drug accumulates in fat tissue. It is eliminated mainly by the kidneys with a half-life of 18-159 days. Common side effects include anorexia, nausea, lethargy, sleepiness and skin problems. 

The observation that mitotane (Lysodren) could produce adrenocortical necrosis in animals led to its use in the palliation of inoperable adrenocortical adenocarcinomas. A reduction in both tumor size and adrenocortical hormone secretion can be achieved in about half of the patients taking the drug. Because normal adrenocortical cells also are affected, endogenous glucocorticoid production should be monitored and replacement therapy administered when appropriate. 

Mitotane is incompletely absorbed from the gastrointestinal tract after oral administration. However, once absorbed, it tends to accumulate in adipose tissue. Mitotane is slowly excreted and will appear in the urine for several years. The major toxicities associated with its use are anorexia, nausea, diarrhea, lethargy, somnolence, dizziness, and dermatitis. 

Mitotane (Lysodren) produces selective atrophy of the zona fasciculata and zona reticularis, which results in a decrease in the secretion of 17-hydroxy corticosteroids. Direct inhibition of cholesterol side-chain cleavage and 11 (3/18-hydroxylase activities has also been demonstrated. Mitotane is capable of inducing remission of Cushing s disease, but only after several weeks of therapy and at the price of severe gastrointestinal distress. Moreover, more than half of patients relapse following cessation of therapy. Other side effects include lethargy,... 

Mitotane, being closely related to the organochlo-rine insecticides, shares its inductive effects on the fiver microsomal drug-metabolizing enzyme system, and its use may therefore alter the requirement for concomitantly administered drugs that are also metabolized by this pathway. 

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