What is mitotane used for?: A Comprehensive Overview

Mitotane, a derivative of the insecticide DDT, has been used since 1959 to treat certain adrenal gland conditions. The antineoplastic agent, also known by the brand name Lysodren, is primarily used for what is mitotane used for? The treatment of adrenocortical carcinoma and off-label management of Cushing's syndrome, by controlling excessive hormone production. Its specific mechanism involves both targeted cell destruction and steroid synthesis inhibition within the adrenal cortex.

Quick Summary

Mitotane is a specialized adrenocorticolytic and antineoplastic drug used for adrenocortical carcinoma and some cases of Cushing's syndrome. It works by inhibiting hormone production and destroying adrenal cortex cells, requiring close monitoring due to its narrow therapeutic window and potential adverse effects.

Key Points

• Primary Indication: Mitotane is the only specifically approved drug for treating adrenocortical carcinoma (ACC), used for advanced, inoperable, or recurrent disease.

• Adjuvant Use: It serves as an adjuvant therapy after surgery in high-risk ACC patients to prevent or delay recurrence.

• Off-Label for Cushing's Syndrome: Mitotane is used off-label to control excessive cortisol production in certain cases of Cushing's syndrome, particularly when other treatments fail.

• Dual Mechanism of Action: The drug works by directly destroying adrenal cortex cells (adrenolytic effect) and by inhibiting enzymes involved in hormone synthesis.

• Complex Pharmacokinetics: It has a long half-life due to accumulation in fat tissue, a narrow therapeutic window, and requires dose adjustments and regular blood-level monitoring for optimal and safe use.

• Risk of Adrenal Insufficiency: A major risk is that mitotane can cause adrenal insufficiency, necessitating high-dose glucocorticoid replacement for all patients.

• Combination Therapy for Advanced ACC: For advanced ACC, it is often combined with other chemotherapy agents like etoposide, doxorubicin, and cisplatin (EDP) to enhance therapeutic effect.

Mitotane's Primary Indication: Adrenocortical Carcinoma

Mitotane (Lysodren) holds a central role in the systemic treatment of adrenocortical carcinoma (ACC), a rare and aggressive cancer of the adrenal glands. It is the only drug specifically approved for this condition. Its use is indicated in various stages of ACC, particularly when the disease is advanced, unresectable, or has metastasized. Mitotane's cytotoxic effect targets the adrenal cortex, including both cancerous and some healthy cells.

Adjuvant Therapy for High-Risk Patients

Mitotane is also used as an adjuvant therapy following surgery for patients with ACC who are at high risk of recurrence. While this specific use is often considered off-label, it is recommended by several treatment guidelines, including those endorsed by the European Society of Endocrinology (ESE) and the European Network for the Study of Adrenal Tumours (ENSAT). The goal of adjuvant therapy is to eliminate any microscopic cancer cells that might remain after surgery, potentially delaying or preventing disease relapse. For optimal effectiveness, therapeutic plasma concentrations of mitotane must be reached and maintained, which can be a slow process.

Mitotane's Off-Label Use in Cushing's Syndrome

In addition to its role in adrenal cancer, mitotane is sometimes used off-label to treat Cushing's syndrome, a condition caused by the body producing too much cortisol. Mitotane's ability to inhibit steroid synthesis and destroy adrenal tissue helps control the excessive hormone production in these patients.

• Controlling Hypercortisolism: Mitotane can be effective in normalizing cortisol levels in a significant portion of Cushing's syndrome patients.
• Used for Resistant Cases: Due to its potential for serious side effects and the availability of better-tolerated alternatives, mitotane is typically reserved for patients who have not responded adequately to other treatments.
• Slow Onset of Action: The time it takes for mitotane to effectively control cortisol levels can be several months, meaning it is not suitable for situations requiring immediate hormonal control.

How Mitotane Works: Mechanism of Action

Mitotane exerts its effects through a dual mechanism that targets the adrenal cortex. This includes a direct adrenocorticolytic effect and the inhibition of specific enzymes involved in steroid hormone production.

1. Adrenocorticolytic Activity: Mitotane directly damages and kills cells in the adrenal cortex, a process known as adrenolysis. It primarily affects the zona fasciculata and zona reticularis, which are responsible for producing cortisol and an... (text truncated due to character limit)

Frequently Asked Questions

What is the brand name for mitotane?

The brand name for mitotane is Lysodren.

Why do patients taking mitotane need steroid replacement?

Mitotane destroys adrenal gland cells and also speeds up the breakdown of corticosteroids, which leads to adrenal insufficiency. Patients must take replacement steroid hormones, such as hydrocortisone, to prevent a life-threatening adrenal crisis.

How is mitotane absorbed and should it be taken with food?

Mitotane is an oral tablet that is better absorbed when taken with a high-fat meal or snack. Taking it with fatty food also helps to reduce common gastrointestinal side effects like nausea and vomiting.

What are the most common side effects of mitotane?

The most common side effects include gastrointestinal issues (nausea, vomiting, diarrhea), neurological symptoms (dizziness, lethargy), skin rash, and endocrine problems like adrenal insufficiency and high cholesterol.

Is mitotane safe during pregnancy?

No, mitotane is teratogenic and can harm an unborn baby. Female patients of reproductive age must use effective, non-hormonal contraception during and for a specific period after treatment concludes.

Why is regular blood monitoring necessary during mitotane treatment?

Regular monitoring of blood mitotane levels is crucial because the drug has a narrow therapeutic window and a long, variable half-life. Monitoring ensures levels are high enough for efficacy but low enough to avoid serious toxicity, especially neurotoxicity.

Can mitotane be used for adrenal cancer in children?

Yes, mitotane can be used to treat adrenocortical carcinoma in pediatric patients. However, given the rarity of the disease and the potential side effects, treatment requires close supervision by a specialized team.