Lysodren (mitotane) / Perrigo Company - LARVOL DELTA

Extended survival in stage IV adrenocortical carcinoma with recurrence and bone metastases. (PubMed, BMJ Case Rep) - "Remission was obtained with radiotherapy, chemotherapy, bone resorptive inhibitors, mitotane and repeat radiofrequency ablation. He was discharged from regular surveillance and remains alive and free of active disease 14 years after initial diagnosis. To our knowledge, this is the longest recorded survival of a patient with stage IV ACC with recurrent disease and bone metastases."

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

Novel inhibitors of BCRP and P-gp found among drugs used in the treatment of cancer (AACR 2026) - "Of the investigated compounds, cabozantinib (IC50 of 0.65 µM), midostaurin (0.69 µM), and entrectinib (5.8 µM) showed the strongest inhibition of BCRP. Nilotinib (1.0 µM), osimertinib (2.0 µM), and abemaciclib (2.4 µM) showed the strongest inhibition of the P-gp. The highest I2/IC50 ratios for BCRP were observed for mitotane (6190), cabozantinib (1730), and abiraterone (831). For P-gp, the highest I2/IC50 ratios were observed for nilotinib (2880), pazopanib (1580), and mitotane (1480)...The highest I1/IC50 ratios for BCRP were observed for doxorubicin (8.2), etoposide (2.8), and fosaprepitant (0.84). For P-gp, the highest I1/IC50 ratios were observed for amscarine (1.6), vinorelbine (0.55), and fosaprepitant (0.50)...Mechanistic static model for BCRP inhibitors suggested that cabozantinib, midostaurin, and apalutamide could almost fully inhibit intestinal BCRP, increasing the exposure to concomitantly administered rosuvastatin by 94%, 89%,..."

Breast Cancer • Oncology • Solid Tumor

Etomidate, Ketoconazole, and Mitotane for Cushing Disease due to Adrenocortical Carcinoma (SCCM 2026) - "Triple therapy (carboplatin, etoposide, and doxorubicin) was considered but not initiated due to poor functional status...Osilodrostrat, mifepristone, metyrapone, and pasireotide were considered but restricted by primary disease and cost...EI's are safe and effective to reduce cortisol quickly, but many institutions and staff are unfamiliar with its use as a continuous infusion. Many challenges still exist for this difficult and rare disease."

Adrenal Cortex Carcinoma • Cushing’s Disease • Diabetes • Endocrine Disorders • Genito-urinary Cancer • Oncology • Rare Diseases • Solid Tumor

From Trial to Practice: No Survival Benefit from Adjuvant Mitotane in Low-Risk Adrenocortical Carcinoma, Insights from a Nationwide Cohort (AUA 2026) - No abstract available

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

Temozolomide as second and subsequent lines of treatment in metastatic adrenocortical cancer. Single-center retrospective trial (Sarcoma-RC 2026) - "A retrospective data showed that the combination of temozolomide (Tem) and mitotane (M) demonstrated promising results. Legal entity responsible for the study Zhulikov Yaroslav yarikzhulikov@gmail.com. Funding Has not received any funding."

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

Prognostic value of DNA methylation profiles in resectable adrenocortical carcinomaprognostic value of DNA methylation profiles in resectable adrenocortical carcinoma (Sarcoma-RC 2026) - "Adjuvant therapy with mitotane was administered to 8 pts (18.6%)...Legal entity responsible for the study Zhulikov Yaroslav yarikzhulikkov@gmail.com. Funding Has not received any funding."

Epigenetic controller • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • GSTP1 • IGF2 • PYCARD

Current clinical management and outcome of patients with adrenal cortical carcinoma (ACC) with rare histological subtypes-an ENSAT cohort study. (PubMed, ESMO Open) - "Stage-adjusted outcome in oncocytic ACC is better than in other subtypes."

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

Clinical Predictors of Outcome in Advanced Adrenocortical Carcinoma: a multicentre international ENSAT study. (PubMed, Eur J Endocrinol) - "The ENSAT Risk Score for Advanced ACC is a practical, prognostic tool for patients with advanced ACC receiving systemic therapy. Based on accessible clinical and biochemical markers, it can support treatment decisions and facilitate informed discussions in routine care."

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

Successful Management of Ectopic Adrenocorticotropin-Secreting Thymic Carcinoid With Mitotane: A New Look at an Old Drug. (PubMed, JCEM Case Rep) - "Other EAS cases treated with MTT reported in the literature were reviewed, and the time needed to control hypercortisolism using MTT was shorter than previously reported. Instead of an "add-on drug," we should reconsider the role of MTT in the treatment of severe hypercortisolism in EAS."

Journal • CNS Disorders • Cushing’s Disease • Endocrine Disorders • Infectious Disease • Mental Retardation • Neuroendocrine Tumor • Oncology • Psychiatry • Solid Tumor • Thymus Cancer

Time trends in incidence, treatment and survival of patients with adrenocortical carcinoma, a nationwide study. (PubMed, J Clin Endocrinol Metab) - "The incidence of adrenocortical carcinoma is stable over time. The five-year survival for stage I-III remained stable, while the survival for stage IV increased. Factors associated with increased survival are centralization of care, adrenalectomy, surgical control of disease, chemotherapy and mitotane therapy."

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

Targeting ER stress in adrenocortical carcinoma: Celastrol as a novel therapeutic candidate. (PubMed, Biomed Pharmacother) - "identifying agents capable of complementing or replacing standard therapy remains a central challenge in ACC research. Our findings suggest that celastrol is a potent bioactive compound with activity against both monolayer and 3D ACC models, offering potential translational relevance. By elucidating ER stress as a shared mechanism between celastrol and mitotane, our work supports further exploration of this pathway as a strategy to potentially improve therapeutic outcomes in ACC patients."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • ATF3 • ATF4

Exceptional Response to a Single Dose of Pembrolizumab as Salvage Therapy for Metastatic Adrenocortical Carcinoma. (PubMed, JCEM Case Rep) - "The patient was started on mitotane and metyrapone, followed by 8 cycles of etoposide-doxorubicin-cisplatin plus mitotane. The patient underwent complete surgical resection, achieving full remission. More than 1 year later, she remains disease free."

Journal • Tumor mutational burden • Adrenal Cortex Carcinoma • Cardiovascular • Cushing’s Disease • Endocrine Disorders • Genito-urinary Cancer • Hypertension • Metabolic Disorders • Oncology • Ovarian Cancer • Solid Tumor • PD-L1 • TMB • 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

ACCOMPLISH: Phase II Trial of Pembrolizumab Plus Lenvatinib in Advanced Adrenal Cortical Carcinoma (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: National Cancer Center, Korea | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Aug 2026 ➔ Feb 2027 | Trial primary completion date: Aug 2025 ➔ Feb 2027

Enrollment closed • Trial completion date • Trial primary completion date • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Preclinical evaluation of progesterone combined with EDP-M scheme in 2D and 3D models of adrenocortical carcinoma. (PubMed, Biomed Pharmacother) - "Overall, these findings confirm the potential role of Pg in improving EDP-M cytotoxic effects in 2D and 3D ACC models."

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

EO2401 (E) peptide immunotherapy + nivolumab (N) in adrenocortical carcinoma (ACC) and metastatic pheochromocytoma/paraganglioma (MPP): EOADR1-19/SPENCER (ESMO 2023) - P1/2 | "Post-hoc analyses identified predictors of lack of efficacy (no mitotane, ECOG > 1, ACC 1st diagnosis ≤9 months(mo), lesion size >125 mm, >3 organs involved, lymphopenia >grade 1); C2-post hoc group was created applying these factors. Conclusions EO2401/N was well tolerated generating durable immune responses correlating with efficacy. Based on the greater efficacy in C2-post hoc group a randomized extension is currently recruiting."

IO biomarker • Metastases • Adrenal Cortex Carcinoma • CNS Tumor • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • BIRC5 • CD4 • CD8 • FOXM1 • IL13RA2 • MSI • PD-L1

Cabozantinib plus atezolizumab in locally advanced/metastatic adrenocortical carcinoma: Results from a multi-cohort basket phase II trial, CABATEN/GETNE-T1914. (ASCO-GU 2024) - P2 | "Patients with locally advanced / metastatic ACC, ≥18 years old and ECOG 0-1 were included after progression to chemotherapy and/or mitotane... Cabozantinib plus atezolizumab showed modest activity in locally advanced/metastatic ACC. Safety profile was consistent with previous reports. The existence of long lasting responders makes it worthwhile to continue investigating predictive factors that help select patients for this combination."

Metastases • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

Adrenocortical carcinoma (ACC): current surgical treatment strategies (PubMed, Chirurgie (Heidelb)) - "Postoperatively, adjuvant therapy is tailored according to individual risk profiles, with mitotane indicated for patients at intermediate or high risk of recurrence...In metastatic disease, multimodal treatment strategies-integrating surgical, interventional radiologic, and systemic approaches-play a central role. Although the overall prognosis remains limited, surgical expertise and treatment within specialized centers are the key for improved patient outcomes."

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

A clinical trial of Tetrandrine Tablets in combination with Mitotane for the treatment of mitotane-resistant advanced adrenocortical carcinom (ChiCTR) - P=N/A | N=62 | Not yet recruiting | Sponsor: West China Hospital of Sichuan University; West China Hospital of Sichuan University

New trial • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

A nonfunctional adrenal incidentaloma revealed by intestinal obstruction: metastatic adrenocortical carcinoma diagnosed by surgery. (PubMed, Endocrinol Diabetes Metab Case Rep) - "Postoperatively, the patient recovered uneventfully and was started on mitotane therapy after PET imaging confirmed residual disease and para-aortic lymph node metastasis...R0 resection remains the only potentially curative treatment for ACC; in selected cases, synchronous resection of metastatic lesions may be necessary. This case highlights a previously undocumented presentation of ACC manifesting as small bowel obstruction due to intestinal metastasis, thereby expanding the clinical spectrum of this rare entity."

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

In Silico Hazard Assessment of Ototoxicants Through Machine Learning and Computational Systems Biology. (PubMed, Toxics) - "We compared predicted environmental ototoxicants with ototoxic drugs, paired select polychlorinated biphenyls with the antineoplastic drug mitotane, and used PCB 177 as a case study to construct an ototoxicity pathway...Findings indicate overlapping mechanisms involving metabolic, cellular, and inflammatory processes. This work shows that integrated computational modeling can support virtual screening and prioritization for chemical and drug ototoxicity risk assessment."

Journal • Oncology • Otorhinolaryngology

Ectopic Adrenocortical Cancer Originating From the Pancreas: A Case Report With Literature Review. (PubMed, Int J Surg Pathol) - "Mitotane and glucocorticoid replacement therapy were added to the patient's treatment plan for ACC...To our knowledge, this is the first reported example of ectopic ACC arising in the pancreas, diagnosed in a 57-year-old patient. ACCs should be considered in the differential diagnosis of tumors arising in nonadrenal regions."

Journal • Adrenal Cortex Carcinoma • Breast Cancer • Cardiovascular • Genito-urinary Cancer • Hypertension • Oncology • Pancreatic Cancer • Solid Tumor

Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study. (PubMed, Lancet Diabetes Endocrinol) - P3 | "Adjuvant mitotane might not be indicated in patients with low-grade, localised adrenocortical carcinoma considering the relatively good prognosis of these patients, and no significant improvement in recurrence-free survival and treatment-associated toxicity in the mitotane group. However, the study was discontinued prematurely due to slow recruitment and cannot rule out an efficacy of treatment."

Journal • Observational data • P3 data • Adrenal Cortex Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Cabozantinib monotherapy for advanced adrenocortical carcinoma: a single-arm, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "Cabozantinib in advanced adrenocortical carcinoma showed promising efficacy with a manageable and anticipated safety profile. Further prospective studies with cabozantinib alone and in combination with immune checkpoint therapy are ongoing."

Journal • Metastases • Monotherapy • P2 data • Adrenal Cortex Carcinoma • Cardiovascular • Genito-urinary Cancer • Hypertension • Oncology • Renal Disease • Solid Tumor

Editorial Comments to Impact of Adjuvant Radiotherapy and Mitotane on Survival in Localized Adrenocortical Carcinoma: A Retrospective Cohort Study. (PubMed, Int J Urol) - No abstract available

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