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Mitotane

Mitotane is a drug being studied in clinical trials for the treatment of adrenocortical carcinoma (ACC), a rare and aggressive cancer of the adrenal glands. These trials aim to evaluate the effectiveness and safety of mitotane alone or in combination with other therapies for patients with ACC at various stages. The research explores mitotane’s potential to improve survival, reduce recurrence risk, and enhance quality of life for those affected by this challenging disease.

Table of Contents

What is Mitotane?

Mitotane is a medication primarily used in the treatment of adrenocortical carcinoma (ACC), which is a rare cancer that affects the outer layer of the adrenal glands. These glands sit on top of the kidneys and are responsible for producing important hormones in the body. Mitotane is known by several other names, including:[1][2]

  • Lysodren
  • o,p’-DDD
  • DDD
  • 1,1-Dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane
  • 2,2-Bis(2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane
These alternative names may appear on your prescription or in medical literature, but they all refer to the same medication.

What Conditions Does Mitotane Treat?

Mitotane is primarily used to treat:[1][3]

  • Adrenocortical Carcinoma (ACC): This is the main condition for which mitotane is prescribed. It can be used in various stages of ACC, including:
    • After surgery to remove the tumor (adjuvant therapy) to reduce the risk of the cancer coming back
    • For advanced or metastatic ACC that cannot be completely removed by surgery
    • For ACC that has spread to other parts of the body
In some cases, mitotane has also been studied for use in other conditions, such as:[2]
  • Prostate Cancer: Some clinical trials have explored the potential use of mitotane in treating advanced prostate cancer, although this is not a standard treatment.
It’s important to note that mitotane is a specialized medication and is typically prescribed by endocrinologists or oncologists who have experience in treating adrenal gland disorders and cancers.

How Does Mitotane Work?

Mitotane works in several ways to combat adrenocortical carcinoma:[1][3]

  • Adrenolytic Activity: Mitotane has a toxic effect on adrenal gland cells. This means it can directly kill cancer cells in the adrenal cortex.
  • Hormone Suppression: It reduces the production of adrenal hormones, particularly cortisol. This can be beneficial because some ACCs produce excess hormones that can cause additional health problems.
  • Altering the Tumor Environment: By changing the hormonal environment around the tumor, mitotane may make the cancer cells more vulnerable to other treatments.
In some cases, the cortisol-lowering effect of mitotane may also enhance the effectiveness of other cancer treatments, such as immunotherapy.

How is Mitotane Administered?

Mitotane is typically given as an oral medication in the form of tablets. The dosing can vary depending on the specific situation, but a common approach is:[1][2]

  • Starting at a lower dose, often around 1.5 to 2 grams per day
  • Gradually increasing the dose over several days or weeks, depending on how well you tolerate the medication
  • The target dose is often between 6 to 10 grams per day, divided into multiple doses throughout the day
Your doctor will adjust the dose based on your blood levels of mitotane and how well you tolerate the medication. It’s crucial to take mitotane exactly as prescribed and to attend all follow-up appointments for monitoring.

Mitotane in Clinical Trials

Mitotane has been and continues to be studied in various clinical trials to better understand its effectiveness and optimal use. Some key trials include:[1][4][5]

  • ADIUVO Trial: This study is looking at the effectiveness of mitotane as an adjuvant treatment (after surgery) in patients with ACC who have a low to intermediate risk of recurrence.
  • FIRM-ACT Trial: This trial compared mitotane combined with a chemotherapy regimen (etoposide, doxorubicin, and cisplatin) to mitotane combined with streptozocin in patients with advanced ACC.
  • Combination Therapy Trials: Several studies are exploring the use of mitotane in combination with other treatments, such as immunotherapy (pembrolizumab) or other chemotherapy drugs.
These trials help researchers understand how to best use mitotane, what combinations of treatments might be most effective, and how to manage side effects.

Potential Side Effects

Like all medications, mitotane can cause side effects. Some common side effects include:[1][3]

  • Gastrointestinal issues: nausea, vomiting, diarrhea, loss of appetite
  • Neurological effects: dizziness, confusion, sleepiness
  • Skin rashes
  • Hormonal changes: decreased levels of cortisol and other adrenal hormones
It’s important to report any side effects to your healthcare team. They can often be managed by adjusting the dose or providing supportive treatments.

Monitoring During Treatment

When you’re taking mitotane, your doctor will closely monitor several aspects of your health:[1][3]

  • Blood Levels of Mitotane: Regular blood tests will be done to ensure the amount of mitotane in your body is in the therapeutic range (usually 14-20 mg/L).
  • Hormone Levels: Your doctor will check your cortisol and other hormone levels to ensure they’re not too low.
  • Liver Function: Mitotane can affect liver enzymes, so these will be monitored.
  • Cholesterol Levels: Mitotane can increase cholesterol, so this will be checked periodically.
These regular check-ups are crucial for ensuring the treatment is effective and safe.

Mitotane in Combination Therapy

Mitotane is often used in combination with other treatments, especially for advanced ACC. Some common combinations include:[4][5]

  • Mitotane + EDP: This combines mitotane with a chemotherapy regimen of etoposide, doxorubicin, and cisplatin. This is often considered the standard first-line treatment for advanced ACC.
  • Mitotane + Immunotherapy: Ongoing trials are exploring the combination of mitotane with immunotherapy drugs like pembrolizumab.
  • Mitotane + Streptozocin: This combination has been studied as an alternative to the EDP combination.
The choice of combination depends on various factors, including the stage of the cancer, your overall health, and the specific characteristics of your tumor. Your oncologist will discuss the most appropriate treatment plan for your individual case.

Aspect Details
Primary Use Treatment of adrenocortical carcinoma (ACC)
Administration Oral, daily dosing
Target Blood Level 14-20 mg/L in many trials
Common Combinations Cisplatin, etoposide, doxorubicin, immunotherapy
Treatment Duration Varies; up to 2 years or until disease progression
Key Outcomes Measured Progression-free survival, overall survival, tumor response
Patient Populations Various stages of ACC, including adjuvant and metastatic settings
Monitoring Regular blood tests, imaging scans, side effect assessment

FAQ

  • What is mitotane and how does it work? Mitotane is a medication used to treat adrenocortical carcinoma. It works by reducing the amount of cortisol produced by the adrenal glands and has a direct toxic effect on adrenal tumor cells. Mitotane is believed to help stop the growth and spread of cancer cells.
  • How is mitotane administered in clinical trials? In most trials, mitotane is given orally (by mouth) daily. The dosage is often started low and gradually increased based on the patient's tolerance and blood levels. Some studies aim for a target blood concentration of 14-20 mg/L.
  • What are the potential side effects of mitotane? Common side effects may include gastrointestinal issues, dizziness, and fatigue. Mitotane can also affect hormone levels, so patients often need hormone replacement therapy. Regular monitoring of blood levels and side effects is important during treatment.
  • Is mitotane used alone or in combination with other treatments? Clinical trials are exploring both mitotane as a single agent and in combination with other therapies. Some studies combine mitotane with chemotherapy drugs like cisplatin and etoposide, while others are investigating its use with immunotherapy or targeted therapies.
  • How long do patients typically take mitotane in clinical trials? The duration of mitotane treatment varies between trials. Some studies administer mitotane for up to 2 years in the adjuvant setting (after surgery), while others continue treatment until disease progression or unacceptable toxicity in advanced cases.

Ongoing Clinical Trials on Mitotane

  • Study on Cemiplimab and Mitotane for Patients with Advanced Adrenocortical Cancer

    Recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    Italy

  • Study of Dostarlimab for Patients with Advanced or Metastatic Non-Colorectal/Non-Endometrial Cancer with dMMR/MSI, Compared to Standard Drug Combination

    Recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    France

  • Study on Mitotane Alone or with Cisplatin and Etoposide for Patients with High-Risk Adrenocortical Carcinoma After Surgery

    Recruiting

    3 1 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany Sweden

  • Study on the Effectiveness of Adding Progesterone to Chemotherapy with Etoposide, Doxorubicin, Cisplatin, and Mitotane for Advanced Adrenocortical Carcinoma Patients

    Not yet recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    Italy

Glossary

  • Adrenocortical Carcinoma (ACC): A rare, aggressive cancer that develops in the outer layer of the adrenal glands.
  • Mitotane: A medication used to treat adrenocortical carcinoma that reduces cortisol production and has a direct toxic effect on adrenal tumor cells.
  • Adjuvant therapy: Additional treatment given after the primary treatment (usually surgery) to lower the risk of cancer recurrence.
  • Progression-free survival (PFS): The length of time during and after treatment that a patient lives without the cancer getting worse.
  • Overall survival (OS): The length of time from the start of treatment or diagnosis that patients are still alive.
  • RECIST criteria: Response Evaluation Criteria in Solid Tumors, a set of rules used to measure cancer response to treatment in clinical trials.
  • Pharmacokinetics: The study of how a drug is absorbed, distributed, metabolized, and eliminated by the body.
  • Immunotherapy: A type of cancer treatment that helps the immune system fight cancer.
  • Targeted therapy: A type of treatment that uses drugs to target specific genes or proteins involved in cancer growth and survival.
  • Quality of life (QoL): A measure of a patient's overall well-being and ability to function in daily life during cancer treatment.

References

  1. https://clinicaltrials.gov/study/NCT00777244
  2. https://clinicaltrials.gov/study/NCT02057237
  3. https://clinicaltrials.gov/study/NCT05344027
  4. https://clinicaltrials.gov/study/NCT05634577
  5. https://clinicaltrials.gov/study/NCT00778817