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Why Lysodren

Lysodren® is the first and only FDA-approved systemic therapy for inoperable adrenocortical carcinoma (ACC)1

  • For the treatment of inoperable, functional or nonfunctional, ACC
  • Demonstrated to be the cornerstone systemic therapy of advanced ACC

Clinical Data

Demonstrated Efficacy in Advanced ACC: Lysodren® Plus Combination Chemotherapy (EDP or etoposide, doxorubicin and cisplatin) in Metastatic ACC2*

 

*The above FIRM-ACT (First International Randomised Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment) Trial is an international phase 3 trial in metastatic ACC which studied the combination of Lysodren® + EDP (etoposide, doxorubicin and cisplatin) (ITT, n=151) vs treatment with Lysodren® + Sz (streptozotocin) (ITT, n=153). PFS and ORR were significantly improved with Lysodren® + EDP vs Lysodren® + Sz. Primary end point of the study: overall survival. Secondary end points: progression-free survival, tumor response, and quality of life.

Demonstrated Efficacy in Advanced ACC: Lysodren® Monotherapy in Advanced ACC3*

 

Lysodren® Is Recommended in International Clinical Practice Guidelines

Endocrinology and Oncology Guidelines Recommend Lysodren® for the Treatment of Advanced ACC.

NCCN Clinical Practice Guidelines in Oncology V1.0 20234

LOCOREGIONAL UNRESECTABLE/METASTATIC ACC
Preferred Regimens
• Carboplatin + etoposide ± doxorubicin ± mitotane (Lysodren®)
• Cisplatin + etoposide ± doxorubicin ± mitotane (Lysodren®)
Other Recommended Regimens
• Mitotane (Lysodren®) monotherapy
• Pembrolizumab ± mitotane (Lysodren®)

ESE-ENSAT Clinical Practice Guidelines 20185*

ADVANCED ACC NOT AMENABLE TO RADICAL RESECTION
mitotane (Lysodren®) is the treatment of choice as either mitotane (Lysodren®) monotherapy or mitotane (Lysodren®) + EDP depending on prognostic parameters (+++O)

*The quality of evidence behind the recommendations is classified as very low (+OOO), low (++OO), moderate (+++O), and strong (++++).

ESMO-EURACAN Clinical Practice Guidelines 20206

ADVANCED/METASTATIC ACC
mitotane (Lysodren®) monotherapy or in combination with chemotherapy

How Lysodren® Works

The 2 main biological effects Lysodren® exhibits are:

1

Direct cytotoxic effect on adrenocortical cells1

2

Decrease in the production of steroids, including cortisol, androgens, and dehydroepiandrosterone from the adrenal cells1

In particular, its metabolites inhibit several enzymes in the adrenocortical steroidogenesis pathway, mainly at the level of the cholesterol side-chain cleavage enzymes CYP11A1 and CYP11B1.7 By inhibiting CYP11A1 and CYP11B1 and together with its adrenolytic effects, Lysodren® may lead to some control of hormone secretion,8 which may further benefit patients with functioning ACC.

The precise mechanism of its antitumor action is not fully understood.

  1. Shirley M. Mitotane in adrenocortical carcinoma: a profile of its use. Drugs Ther Perspect. 2022;38:508-519. doi:10.1007/s40267-022-00958-y
  2. Fassnacht M, Terzolo M, Allolio B, et al. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012;366(23):2189-2197. doi:10.1056/NEJMoa1200966
  3. Megerle F, Herrmann W, Schloetelburg W, et al. Mitotane monotherapy in patients with advanced adrenocortical carcinoma. J Clin Endocrinol Metab. 2018;103(4):1686-1695. doi:10.1210/jc.2017-02591
  4. Neuroendocrine and Adrenal Tumors. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). NCCN. August 2, 2023; Version 1.2023.
  5. Raj N, Zheng Y, Kelly V, et al. PD–1 blockade in advanced adrenocortical carcinoma. J Clin Oncol. 2020;38(1):71-80. doi:10.1200/JCO.19.01586
  6. Habra MA, Stephen B, Campbell M, et al. Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma. J Immunother Cancer. 2019;7(1):253. doi:10.1186/s40425-019-0722-x
  7. Fassnacht M, Dekkers O, Else T, et al. European society of endocrinology clinical practice guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European network for the study of adrenal tumors. Eur J Endocrinol. 2018;179(4):G1-46. doi:10.1530/EJE-18-0608
  8. Fassnacht M, Assie G, Baudin E, et al. Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(11):1476-1490. doi:10.1016/j.annonc.2020.08.2099
  9. Libé R. Adrenocortical carcinoma (ACC): diagnosis, prognosis, and treatment. Front Cell Dev Biol. 2015;3:45. doi:10.3389/fcell.2015.00045
  10. Else T, Kim AC, Sabolch A, et al. Adrenocortical carcinoma. Endocr Rev. 2014;35(2):282-326. doi:10.1210/er.2013-1029
  11. Baudin E, Leboulleux S, A Al Ghuzlan, et al. Therapeutic management of advanced adrenocortical carcinoma: what do we know in 2011? Horm Cancer. 2011;2(6):363-371. doi:10.1007/s12672-011-0094-2
  12. Lysodren®. US Prescribing information. ESTEVE.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR LYSODREN©
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Warning/Adrenal crisis in the setting of shock, severe trauma or infection: Patients treated with LYSODREN are at increased risk for developing adrenal crisis in the setting of shock, severe trauma or infection that may lead to death. If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. Monitor patients closely for infections and instruct patients to contact their physician immediately if injury, infection, or any other concomitant illness occurs.
LYSODREN® is an adrenal cytotoxic agent indicated for the treatment of patients with inoperable, functional or nonfunctional, adrenocortical carcinoma (ACC).

Warning/Adrenal crisis in the setting of shock, severe trauma or infection: Patients treated with LYSODREN are at increased risk for developing adrenal crisis in the setting of shock, severe trauma or infection that may lead to death.
If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids. Monitor patients closely for infections and instruct patients to contact their physician immediately if injury, infection, or any other concomitant illness occurs.

Adrenal Insufficiency and Adrenal Crisis: Temporarily withhold LYSODREN during shock; trauma, infection or adrenal insufficiency. Steroid replacement may be necessary.

Central Nervous System (CNS) Toxicity: Monitor behavioral and neurologic assessments and mitotane plasma levels at regular intervals. Mitotane plasma levels exceeding 20 mg/L are associated with a greater incidence of toxicity. Advise patients not to drive or operate hazardous machinery if experiencing CNS adverse reactions.

Ovarian Macrocysts in Premenopausal Women: Monitor pelvic ultrasound at baseline and at regular intervals. Withhold, reduce the dose, or permanently discontinue LYSODREN based on severity.

Hematologic Toxicity: Monitor complete blood counts prior to starting LYSODREN, during dose titration and as clinically indicated. Withhold, reduce the dose or permanently discontinue based on severity.

Prolonged Bleeding Time: Prolonged bleeding time has occurred in patients treated with mitotane and this should be taken into account when surgery is considered.

Embryo-Fetal Toxicity: LYSODREN can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective nonhormonal contraception.

Lactation: Advise not to breastfeed.

Hepatic Impairment: LYSODREN is not recommended for patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, monitor mitotane plasma levels frequently and modify the dosage as needed.

Renal Impairment: LYSODREN® is not recommended for patients with severe renal impairment. In patients with mild or moderate renal impairment, monitor mitotane plasma levels frequently and modify the dosage as needed.

Most common adverse reactions include: anorexia, epigastric discomfort, nausea, vomiting diarrhea, depression, dizziness, vertigo, rash, hypercholesterolemia, hypertriglyceridemia, hypothyroidism and decreased blood free testosterone in males. LYSODREN is a hazardous drug. Advise caregivers to wear disposable gloves when handling LYSODREN tablets.

Avoid concomitant use with spironolactone, certain CYP3A substrates, hormonal contraceptives and warfarin.

Please see Full Prescribing Information, including BOXED WARNING, for LYSODREN® (mitotane) tablets.

To report SUSPECTED ADVERSE REACTIONS, contact Direct Success Pharmacy, Inc. at 1-844-LYSODREN (1-844-597-6373) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Link to US Prescribing Information including Boxed Warning.

ESTEVE.
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Tel: +34 93 446 60 00 / Fax: +34 93 347 39 44
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Lysodren a registered trademark of ESTEVE
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Last updated: October 2025; 0097-10/2026@ESTEVE

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