Lysodren (mitotane) / Perrigo Company - LARVOL DELTA

Prolonged Mitotane Administration in Metastatic Adrenocortical Carcinoma With Over a Decade of Survival: A Case Series. (PubMed, Case Rep Endocrinol) - "Metastatic ACC should be managed by multidisciplinary tailored approaches, including close surveillance and local therapies (LT). In patients with LTB, prolonged mitotane therapy can represent a safe option to slow down disease progression and contribute to prolonging survival."

Journal • Adrenal Cortex Carcinoma • Cushing’s Disease • Dyslipidemia • Endocrine Disorders • Genito-urinary Cancer • Oncology • Pain • Solid Tumor

Mitigating subtherapeutic cabozantinib exposure after prior mitotane therapy in adrenocortical carcinoma: Pharmacological boosting with cobicistat. (PubMed, Br J Clin Pharmacol) - "Our findings suggest that an aggressive approach, combining pharmacokinetic boosting, dose escalation and frequent pharmacokinetic monitoring is required to prevent undertreatment and toxicity. By mitigating mitotane-induced subtherapeutic concentrations, this pharmacokinetic strategy may facilitate more effective use and earlier initiation of cabozantinib as second-line treatment in ACC."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Oligometastatic adrenocortical carcinoma: definition and treatment. (PubMed, Curr Opin Oncol) - "If a definition of oligometastatic ACC is required, a reasonable one would include stage IVa disease or up to five metastases <3 cm. Management should rely on a multidisciplinary approach in referral centers, integrating systemic and local therapies to optimize survival and quality of life."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Mitotane, etoposide, doxorubicin, and cisplatin combination treatment in patients with advanced adrenocortical carcinoma: A real-world retrospective analysis of Korean patients (EMUC 2025) - "While M-EDP (mitotane, etoposide, doxorubicin, and cisplatin) showed better outcomes over mitotane plus streptozocin in phase III trial, data on its efficacy and tolerability in Asian populations remain limited. These findings provide valuable real-world evidence for advanced ACC management in Asian populations and reinforce the clinical applicability of M-EDP in this challenging malignancy. This abstract was edited with the assistance of AI technology (ChatGPT) to improve language clarity."

Metastases • Real-world • Real-world evidence • Retrospective data • Genito-urinary Cancer • Oncology • Solid Tumor

Contemporary Approaches to Adrenocortical Carcinoma. (PubMed, Hematol Oncol Clin North Am) - "Advanced disease traditionally relies on mitotane-based chemotherapies to control disease progression. Clinical trials evaluating the potential efficacy of immunotherapy, checkpoint inhibitors, and tyrosine kinase inhibitors are ongoing but have yet to yield results that impact guideline-based therapies. Other therapies, such as radiation, are commonly used for recurrent or metastatic disease."

Journal • Review • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

ADRENOCORTICAL CARCINOMA CRISIS MANAGED WITH STRESS-DOSE STEROIDS (CHEST 2025) - "CASE PRESENTATION: A 48-year-old female with a history of ACC status post-left adrenalectomy with metastasis to lung and liver on pembrolizumab, mitotane, and radiation therapy to the liver presented with fevers, cough, and abdominal pain...Bloodwork revealed an 11-deoxy level of 676 despite mitotane prompting endocrinology to start isturisa... After starting on the stress dose steroids, the patient had a marked improvement leading to a downgrade from ICU. Although not fully understood, ACC is a condition that requires more research to develop treatment plans on an oncologic and endocrine level."

Adrenal Cortex Carcinoma • Cardiovascular • Cough • Cushing’s Disease • Endocrine Disorders • Genito-urinary Cancer • Hepatocellular Cancer • Hypertension • Nephrology • Oncology • Renal Disease • Respiratory Diseases • Solid Tumor • IGF2 • PRKAR1A • TP53

Phase 2 Study of Monotherapy with Pembrolizumab for Advanced Adrenocortical Carcinoma. (PubMed, J Immunother Precis Oncol) - P2 | "All other lines of therapy, including mitotane, were stopped before pembrolizumab initiation. No treatment-related deaths occurred. Single-agent pembrolizumab in the treatment of advanced ACC has potential for durable responses and a manageable safety profile."

Journal • Monotherapy • P2 data • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI

Second-line treatment in patients with advanced adrenocortical carcinoma: A single-center retrospective study (ESMO 2025) - "Exploratory analysis included concurrent mitotane and achievement of targeted plasma levels during second-line treatment. Results Out of 138 reviewed patients with advanced ACC, 45 received second-line chemotherapy: gemcitabine-capecitabine (GemCap, 63%), gemcitabine-docetaxel (GemDoc, 21,7%), temozolomide-capecitabine (TemCap, 11,1%) and 1 patient received pembrolizumab...Further trials are warranted for patients with advanced ACC in this setting. Legal entity responsible for the study P.A. Hertsen Moscow Oncology Research Institute."

Metastases • Retrospective data • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

PHARMACOKINETIC VARIABILITY OF MITOTANE IN PEDIATRIC ADRENOCORTICAL CARCINOMA AND THE ROLE OF CYP2B6 GENOTYPES: A CASE SERIES (SIOP 2025) - "This case series indicates that TDM is needed to dose mitotane within therapeutic window. Our results also suggest that CYP2B6 genotypes could influence the dosage needed. Future studies should investigate dosage regimens in relation to genotyping, with other covariables like intake with fat-rich foods to further explain the pharmacokinetic variability of mitotane."

Clinical • PK/PD data • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Pediatrics • Solid Tumor

AGGRESSIVE SURGERY FOR ADRENAL MALIGNANCIES AND SECRETING PARAGANGLIOMAS IN CHILDREN ACHIEVES BETTER OUTCOMES – A SINGLE CENTRE EXPERIENCE (SIOP 2025) - "ARAR0332 chemotherapy protocols (including mitotane) were needed in 5 cases of ACC... Radical tumour resection with chemotherapy is effective in both locally advanced and metastatic adrenal tumours/SGPs in children. The prognosis for these tumours is not as dismal as the adult experience and an aggressive treatment strategy should be pursued if possible."

Clinical • Surgery • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Pediatrics • Solid Tumor

CLINICAL AND PATHOLOGICAL CHARACTERISTICS OF CHILDREN WITH ADRENOCORTICAL TUMORS: HACETTEPE EXPERIENCE WITH 54 CASES (SIOP 2025) - "Twenty patients received treatment: mitotane only, 5; mitotane/cisplatin/etoposide/doxorubicin 8; mitotane/cisplatin/etoposide,5; cisplatin/doxorubicin, 1; cisplatin/etoposide, 1. For older patients with metastatic disease, novel treatment approaches are needed. Specific management guidelines are required for pediatric ACTs."

Clinical • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Pediatrics

Effectiveness of Medical Treatment on Survivability in Canine Cushing's Syndrome: A Systematic Review and Meta-Analysis. (PubMed, Animals (Basel)) - "Several pharmacological agents are available: trilostane, mitotane, ketoconazole, cabergoline, selegiline, and aminoglutethimide, but their comparative effects on survival remain unclear. In contrast, pooled survival rates at fixed intervals favored trilostane, with an 11% higher survival at 36 months (p = 0.005) and no heterogeneity observed (I2 = 0%). These findings suggest trilostane may offer long-term survival benefits over mitotane."

Journal • Retrospective data • Cushing’s Disease • Endocrine Disorders

A novel therapeutic approach to adrenocortical carcinoma repurposing fingolimod to target sphingolipid metabolism in metastatic disease. (PubMed, Surgery) - "Fingolimod induces apoptosis in adrenocortical carcinoma cells by targeting sphingolipid metabolism and prevents liver and lung metastatic invasion in vitro. Further in vivo validation studies alone or in combination with immune checkpoint inhibitor will support its clinical translation as a novel repurposed therapy in adrenocortical carcinoma."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Metabolic Disorders • Oncology • Solid Tumor

ETOMIDATE AS AN ALTERNATIVE TO ANTIANDROGENIC THERAPY IN A CASE OF HYPERCORTISOLISM (CHEST 2025) - "A number of oral therapies are available to reduce serum cortisol including Ketoconazole, Metyrapone, and Mitotane; however, data regarding intravenous alternatives is limited.In recent years, Etomidate has been studied as an intravenous alternative for antiandrogenic therapy. Without enteral access, conventional oral therapies for hypercortisolism are unavailable. Etomidate should be considered in intubated patients requiring rapid serum cortisol reduction to prevent lapses in antiandrogenic therapy."

Clinical • Adrenal Cortex Carcinoma • Endocrine Disorders • Genito-urinary Cancer • Respiratory Diseases • Solid Tumor

Feminizing Adrenocortical Carcinoma in Men: A Rare Cause of Persistent Gynecomastia and a Contemporary Literature Review. (PubMed, Epidemiologia (Basel)) - "This case illustrates the rare presentation of feminizing adrenocortical carcinoma with reversible infertility and highlights the importance of early recognition and close surveillance. In addition, our literature review of 12 male cases reported between 2015 and 2025 emphasizes gynecomastia as the hallmark presentation and discusses emerging evidence supporting active surveillance as a potential alternative to adjuvant mitotane in selected low-risk patients."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Infertility • Oncology • Sexual Disorders • Solid Tumor

Preclinical evaluation of the antitumoral efficacy of Wee1 inhibitor AZD1775 in adrenocortical carcinoma. (PubMed, Pharmacol Res) - "Current therapy for advanced adrenocortical carcinoma (ACC) is represented by EDP-M (etoposide, doxorubicin, cisplatin + mitotane), but its efficacy is limited and new approaches are needed. Interestingly, Myt1 increase after AZD1775 treatment in primary ACC cells was reverted by EDP-M cotreatment. Overall, our data in in vitro and in vivo preclinical ACC models support AZD1775 as a promising ACC therapeutic option, and its combination with EDP-M as a useful strategy to enhance drug efficacy, reduce cortisol secretion, prevent drug resistance and minimize side effects by reducing the therapeutic dosage."

Journal • Preclinical • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • PKMYT1

Oncocytic Carcinoma: A Rare Hormone-Producing Tumor. (PubMed, Cureus) - "Postoperatively, hypertension and potassium levels normalized with reduced antihypertensive therapy; she commenced steroid replacement and adjuvant mitotane. At early follow‑up, she remained clinically stable and disease‑free. This case highlights the importance of considering OACC in patients with large adrenal masses and resistant hypertension, demonstrates the value of multidisciplinary management and definitive surgery, and contributes to the limited evidence guiding adjuvant therapy for this uncommon tumor."

Journal • Adrenal Cortex Carcinoma • Cardiovascular • Genito-urinary Cancer • Hypertension • Oncology • Pain • Solid Tumor • SYP

Mitotane Treatment for Malignant Leydig Cell Tumor: A Case Report. (PubMed, IJU Case Rep) - "The disease progressed, and the patient died 4 years post-diagnosis and 14 months after starting mitotane. Mitotane shows promise in treating malignant LCTs, but careful management of adverse effects is necessary."

Journal • Anorexia • Fatigue • Oncology • Testicular Cancer

Iron Oxide Nanoparticle Uptake, Toxicity, and Steroidogenesis in Adrenocortical Carcinoma Cells Using a Multicellular in vitro Model. (PubMed, Int J Nanomedicine) - "Surgery and mitotane-based chemotherapy remain the standard of care, and new treatment strategies are needed...However, non-specific uptake by monocytes and endothelial cells reduces delivery efficiency. These findings highlight the need for strategies to enhance tumour-specific targeting and improve biodistribution in future theranostic applications."

Journal • Preclinical • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • MUC1

Frontiers in Systemic Therapy for Unresectable or Metastatic Adrenocortical Carcinoma: Harnessing Novel Therapeutic Approaches. (PubMed, Clin Med Insights Oncol) - "Chemotherapy and mitotane are the traditional systemic therapies of choice. More recently, as drug development in oncology has shifted away from chemotherapy, a host of therapeutic approaches targeting novel mechanisms of action has been studied in adrenocortical carcinoma. This review summarizes all nonchemotherapeutic approaches that have been and/or are currently being tested in clinical trials for the treatment of unresectable or metastatic adrenocortical carcinoma."

Journal • Review • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Evaluation of Side Effects of Mitotane (clinicaltrials.gov) - P=N/A | N=400 | Active, not recruiting | Sponsor: University of Wuerzburg | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Adverse events • Trial completion date • Trial primary completion date • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Mitotane-Induced Endocrine Alterations in Children with Adrenocortical Carcinoma: Clinical Implications from a 20-Year Retrospective Study. (PubMed, Children (Basel)) - "Mitotane therapy in pediatric ACC is strongly associated with significant endocrine dysfunction. These findings emphasize the need for proactive, multidisciplinary endocrine management throughout treatment."

Journal • Retrospective data • Adrenal Cortex Carcinoma • Endocrine Cancer • Endocrine Disorders • Genito-urinary Cancer • Nephrology • Oncology • Pediatrics • Renal Disease • Solid Tumor

Adverse events related to mitotane during treatment of adrenocortical carcinoma. (PubMed, Medicina (B Aires)) - "Mitotane blood concentration in 3 of 4 patients was below the optimal range. Treatment with mitotane requires individualized care to mitigate the risks of adverse events, optimize therapeutic outcomes, and ensure patient safety."

Adverse events • Journal • Adrenal Cortex Carcinoma • Dyslipidemia • Endocrine Disorders • Genito-urinary Cancer • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor

Efficacy and Safety of Radiotherapy and Systemic Treatments in Adrenocortical Carcinoma: Systematic Review and Meta-Analysis. (PubMed, J Clin Endocrinol Metab) - "Mitotane significantly improves survival outcomes in patients with ACC, while radiotherapy exhibits potential benefits, particularly in localized disease. Further research is needed to verify the efficacy of cytotoxic chemotherapy, and randomized controlled trials are required to provide robust evidence of different treatment approaches."

Journal • Retrospective data • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

External validation of the S-GRAS score for predicting recurrence in patients with adrenocortical carcinoma: implications for adjuvant mitotane therapy. (PubMed, Eur J Endocrinol) - "Our findings validate the S-GRAS score in a multicenter cohort and support its use in identifying candidates for adjuvant mitotane. Nonlinear modeling of Ki-67% enhances predictive precision without increasing complexity, but the performance plateau of clinical variables suggests that integrating molecular biomarkers may be necessary to improve prognostic accuracy."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor