Mitotane

Key Terms: Adrenocortex.

Definition

Mitotane (also known by the brand name Lysodren) is a medicine that has been proven to be effective in the treatment of adrenocortical carcinoma.

Purpose

Mitotane destroys cells of the adrenocortex. The adrenocortex, also called the adrenal cortex, is a section of adrenal gland that sits on top of the kidneys. Mitotane is usually used for patients whose cancer cannot be treated surgically and for patients whose cancer has metastasized.

Description

As a chemical, mitotane resembles the insecticides DDD and DDT, although mitotane does not harm people as these do. Scientists do not understand why, but the drug causes damage to the adrenocortex in such a way as to be helpful for some patients with adrenocortical tumors. In addition, mitotane restricts the ability of the gland to produce chemicals.

Recommended Dosage

The dose of mitotane given to patients varies, although between four and eight grams (0.12–0.25 oz) per day is a typical dose. Patients vary in how much mitotane they tolerate, some patients tolerating two grams (0.1 oz) per day while others tolerate sixteen grams (0.5 oz) per day. The doses are given orally. At the beginning of the therapy, the patient may receive 500 milligrams of mitotane twice a day. At any one time a third or a quarter of an entire day's dose is taken. If the patient has difficulty tolerating a certain dose, the doctors may adjust this and use a somewhat smaller dose. Mitotane should be given for at least three months. If the medicine is effective, it may be continued indefinitely. However, most patients respond to the x-ray treatment of the pituitary gland and so do not need mitotane treatment to continue indefinitely.

Many doctors use mitotane in conjunction with radiation therapy directed to the pituitary gland, but other approaches to this medicine may also be taken.

Precautions

Many patients on mitotane should receive adrenocorticosteroids.

Side Effects

Four out of five patients receiving mitotane experience anorexia and nausea. About one-third of patients experience lethargy and sleepiness. Roughly one in five develop skin problems with the medicine. However, patients who experience these side effects do not have to stop taking the medication, although the doctor may lower the dose the person is receiving.

Interactions

Mitotane should not be given with spironolactone (a diuretic/water pill).

—Bob Kirsch

An oral chemotherapeutic agent that causes selective necrosis and atrophy of the adrenocortical zona fasciculata and zona reticularis. Used in the treatment of inoperable adrenal cortical carcinoma in humans and in canine Cushing's syndrome. Called also o,p-DDD.

1 : 1 mixture (racemate) Mitotane
Systematic (IUPAC) name
(RS)-1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)-ethyl]-benzene
Identifiers
CAS number	53-19-0
ATC code	L01XX23
PubChem	4211
DrugBank	APRD00494
Chemical data
Formula	C14H10Cl4
Mol. mass	320.04 g/mol
Pharmacokinetic data
Bioavailability	40%
Protein binding	6%
Metabolism	?
Half life	18 to 159 days
Excretion	?
Therapeutic considerations
Licence data	US FDA:link
Pregnancy cat.	C
Legal status	℞ Prescription only
Routes	Oral
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Mitotane, or o,p'-DDD, is a medication used in the treatment of the rare disease adrenocortical carcinoma.^[1] It is an isomer of DDD and is a derivative of DDT.^[2]

It has been produced by Bristol Myers Squibb SpA but it is marketed as an orphan drug due to the small number of patients in need of it. Its administration occurs in cases where the tumour cannot be surgically omitted. A 2007 study of 177 patients shows a significant increase in the recurrence-free interval after radical surgery followed by Mitotane when compared to surgery alone.^[3]

Mitotane alters steroid peripheral metabolism, directly suppresses the adrenal cortex and alters cortisone metabolism leading to hypocortisolism. Side effects as reported by Schteinberg et al. include anorexia and nausea (88%), diarrhea (38%), vomiting (23%), decreased memory and ability to concentrate (50%), rash (23%), gynecomastia (50%), arthralgia (19%), and leukopenia (7%).^[4]

Its trade name is Lysodren.

Veterinary use

Mitotane is also used to treat pituitary-dependent Cushing's syndrome in canines. The medication is used in the controlled destruction of adrenal tissue, leading to a decrease in cortisol production.^[5]

References

1. ^ Hahner S, Fassnacht M (April 2005). "Mitotane for adrenocortical carcinoma treatment". Current opinion in investigational drugs (London, England : 2000) 6 (4): 386–94. PMID 15898346. 
2. ^ Information from PubChem
3. ^ Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, Rossetto R, Buci L, Sperone P, Grossrubatscher E, Reimondo G, Bollito E, Papotti M, Saeger W, Hahner S, Koschker AC, Arvat E, Ambrosi B, Loli P, Lombardi G, Mannelli M, Bruzzi P, Mantero F, Allolio B, Dogliotti L, Berruti A.. "Adjuvant mitotane treatment for adrenocortical carcinoma". N Engl J Med. 2007 Jun 7;356(23):2372-80.. 
4. ^ Schteinberg DE, Motazedi A, NoonanRA, Thompson NW. "Treatment of Adrenal Carcinomas". Arch.Surg. (1982) 117:1142-9. 
5. ^ Canine Cushing’s Syndrome: Diagnosis and Treatment

External links

• V. P. Komissarenko1, I. S. Chelnakova and A. S. Mikosha. “Effect of o,p-dichlorodiphenyldichloroethane and perthane in vitro on glutathione reductase activity in the adrenals of dogs and guinea pigs.”

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