Lysodren (mitotane) / Perrigo Company - LARVOL DELTA

Beyond mitotane: next-generation therapeutic landscapes in adrenocortical carcinoma. (PubMed, Endocr Oncol) - "Since the FIRM-ACT trial established the combination of etoposide, doxorubicin, and cisplatin plus mitotane (EDP-M) as the frontline standard, overall survival for metastatic patients has remained stubbornly low. This review will address these current immunological hurdles but also explore novel strategies designed to bypass this barrier entirely. By shifting focus towards mechanisms that do not solely rely on the traditional engagement of adaptive immune system - such as the targeted delivery of cytotoxic payloads via antibody-drug conjugates (ADCs) or the androgen-mediated activation of myeloid cells to clear pro-tumoural populations - the field is moving towards a future where the 'cold' nature of the tumour microenvironment may no longer dictate the limits of therapeutic success."

Journal • Review • Adrenal Cortex Carcinoma • 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

A decade of survival in recurrent nonfunctioning oncocytic adrenocortical carcinoma in a young Filipina. (PubMed, JCEM Case Rep) - "She developed local recurrence at 2.5 years, underwent open resection (R1; Ki-67 20%) followed by adjuvant tumor-bed radiotherapy and mitotane, which was discontinued because of intolerance and cost. After a lapse in follow-up, she developed a solitary hepatic metastasis resected with negative margins; planned etoposide, doxorubicin, and cisplatin chemotherapy was stopped after 3 cycles because of ototoxicity...More than 10 years from diagnosis, she remains under active surveillance without radiographic evidence of active disease. This case highlights the potential for prolonged survival in selected patients with recurrent/metastatic ACC through iterative multidisciplinary decision-making, medical management, and repeat metastasectomy when feasible."

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

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

Volumetric Microsampling for Patient-Centric Therapeutic Drug Monitoring in Clinical Pharmacology: A Scoping Review. (PubMed, J Clin Pharmacol) - "Fixed conversion factors performed well for lacosamide and levetiracetam but were less reliable for lamotrigine at high concentrations. Several analyte-matrix combinations, including cefepime, vancomycin, meropenem, paclitaxel, abiraterone, and mitotane, did not consistently meet agreement criteria. Volumetric microsampling can support patient-centered drug monitoring when validated for the specific analyte, matrix, device, and clinical application. Future research should prioritize drug-specific optimization, multicenter validation, standardized conversion reporting, and integration with MIPD platforms."

Journal • Review

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

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

Concomitant parathyroid hormone-secreting oncocytic adrenocortical carcinoma and parathyroid adenoma. (PubMed, JCEM Case Rep) - "Steroid excess resolved and he started mitotane...Staining of the recurrent ACC demonstrated PTH positivity. This is a novel case of PTH-secreting ACC and concomitant parathyroid adenoma."

Journal • Adrenal Cortex Carcinoma • Endocrine Disorders • Genito-urinary Cancer • Metabolic Disorders • Oncology • Solid Tumor • MLH1 • MSH2 • MSH6 • PMS2 • TP53

Severity and management of hypercortisolism in patients with adrenocortical carcinoma and overt Cushing´s syndrome. (PubMed, J Clin Endocrinol Metab) - "Adrenal tumor size and the severity of cortisol excess are associated with a higher probability of metastatic disease at diagnosis. Our study suggests that the severity of cortisol excess appears to be associated with an increased risk of tumor recurrence/progression, suggesting that hypercortisolism intensity may serve as a marker of aggressive disease."

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

Transcriptomic and proteomic signatures predict in vitro response to mitotane in adrenocortical carcinoma. (PubMed, Eur J Endocrinol) - "In summary, transcriptomic and proteomic profiling offers promise to predict mitotane response in ACC. Our findings suggest that responders exhibit features of aggressive ACC, with distinct molecular characteristics that could serve as biomarkers for treatment selection."

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

Mitotane-induced drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome complicated with severe hepatitis. (PubMed, Eur J Dermatol) - No abstract available

Journal • Eosinophilia • Immunology • Inflammation

Does Automated Versus Manual Ki67 Labeling Index Assessment Influence Risk Stratification in Patients with Localized Adrenocortical Carcinoma? Lessons from the ADIUVO Trial. (PubMed, Cancers (Basel)) - "Our findings support the original ADIUVO results and support continued use of manual expert Ki67 LI scoring. This traditional approach remains robust and pragmatic for most clinical settings, especially where automated systems are not readily accessible."

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

Case Report: Low-dose mitotane in a case of recurrent adrenocortical carcinoma: a 20-year clinical perspective. (PubMed, Front Oncol) - "At the latest assessment, the patient remained in good general condition and continued hydrocortisone 40 mg/day, fludrocortisone 0.1 mg/day, and levothyroxine. This case documents sustained disease control during and after almost 20 years of individualized mitotane therapy following recurrent ACC. It emphasizes the importance of dose adaptation, therapeutic drug monitoring, careful endocrine replacement, and cautious interpretation of long-term benefit in a single patient."

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

Evaluation of Curcumin as a Supplement to Improve Mitotane Effects on Adrenocortical Carcinoma. (PubMed, Cells) - "Crucially, in vivo, curcumin administration to tumor-free mice significantly upregulated NRF2 expression and preserved liver tissue integrity. These results warrant further preclinical evaluation of the proposed combination therapy, particularly for those patients who fail to achieve or maintain mitotane plasma concentrations in the therapeutic range."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • HIF1A • NFE2L2

An observational study of menstrual function and related hormones before and after treatment of Cushing syndrome. (PubMed, J Endocr Soc) - "Extensive pituitary exploration, pituitary irradiation, and mitotane reduced the likelihood of menses returning to baseline...In most women with minimal pituitary damage, menses return to baseline after a median of 6 months of eucortisolism. Significant overweight can delay resolution."

Journal • Observational data • Cushing’s Disease • Endocrine Disorders • Obesity • Oncology

Patient Experience of Adrenocortical Carcinoma: Views from a Patient, His Physician and a Patient Association. (PubMed, Adv Ther) - "The endocrinologist provides an evidence-based perspective on treatment decisions, the role of mitotane in long-term disease control, and the need for ongoing replacement therapy with hydrocortisone to manage adrenal insufficiency following extended mitotane treatment. Finally, the patient association representative emphasizes the unmet informational needs of patients with rare cancers and the pivotal role of advocacy organizations in improving patient and physician awareness of ACC, fostering collaboration, and advocating for better education and support for ACC patients and their families and caregivers. Together, these viewpoints emphasize the need to optimize treatment decisions, strengthen patient-physician collaboration, and share long-term insights to guide care in ACC patients with the aim of achieving the best possible outcomes."

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

Frequent antecedent nodules and diagnostic gaps in adrenocortical carcinoma. (PubMed, J Endocr Soc) - "Patients with high-grade disease received more interventions; those who received mitotane and/or locoregional therapies had improved survival (adjusted HR, 0.31; 95% CI, 0.14-0.71, and adjusted HR, 0.47; 95% CI, 0.23-0.98, respectively)...Initial diagnostic evaluation was often incomplete or inappropriately invasive, compromising the preoperative window and patient survival. These findings challenge current surveillance paradigms, revealing an extended but vulnerable window for surgical cure."

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

Real-world safety profile of mitotane in adrenocortical carcinoma: a retrospective cross-sectional study integrating pharmacovigilance and interpretable machine learning. (PubMed, Front Endocrinol (Lausanne)) - "Integrating signal detection, clinical prioritization, and interpretable machine learning reveals multivariable patterns underlying serious AEs. These findings support a risk-stratified monitoring approach to enhance the clinical safety of mitotane therapy."

Adverse events • Journal • Observational data • Real-world evidence • Retrospective data • Adrenal Cortex Carcinoma • Endocrine Disorders • Genito-urinary Cancer • Nephrology • Oncology • Renal Disease • Solid Tumor

A retrospective cohort study of surgery for adrenocortical carcinoma in a tertiary endocrine surgery unit. (PubMed, Ann R Coll Surg Engl) - "This study provides a contemporary perspective on epidemiology and practice in the management of ACC in the UK."

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

Potential therapeutic targets for obstructive sleep Apnea were identified through network pharmacology, WGCNA, machine learning, immune infiltration analysis, and ceRNA network. (PubMed, Integr Biol (Camb)) - "Our current findings provide a rationale for identifying therapeutic targets in the diagnosis and treatment of OSA. In addition, these findings have the potential to facilitate the translation of our study to clinical applications in the future. Insight Box Different from other single-gene predictors of OSA, network pharmacological analysis identified differential genes and explored biomolecular markers of OSA from multi-gene and multi-target perspectives through enrichment analysis, construction of ceRNA gene network, and correlation analysis and explore early genomic diagnostic indicators of OSA and corresponding drug prediction targets using network pharmacological analysis and to elucidate the etiology and pathogenesis of OSA from the genetic level. To provide a more accurate method for the diagnosis, prevention, and treatment of clinical OSA, it is expected to provide a research basis for the accurate diagnosis of clinical OSA and the pathogenesis of OSA."

Journal • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • UQCRC1

Enhanced efficiency in mitotane therapeutic drug monitoring: optimization of chromatographic resolution and column longevity. (PubMed, Clinics (Sao Paulo)) - No abstract available

Journal

Exploring Targets for Heart Failure Using Mendelian Randomization, Colocalization, Summary Data-based Mendelian Randomization, and Drug Prediction. (PubMed, J Vis Exp) - "Moreover, potential drugs targeting these targets were identified using drug prediction and molecular docking, including mitotane, Adehl, Benzofurans, 1,3-Di-o-tolylguanidine, 96-69-5, and bromoenol lactone. Furthermore, PCR results also demonstrated that mitotane might be associated with CYP11A1 and KCNH2. Drugs designed based on these potential therapeutic targets may offer higher success rates and improve clinical outcomes."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • CHD4 • IL1R1 • KCNH2 • LPAR5

Systemic Management of Adrenal Malignancies: Adrenocortical carcinoma and pheochromocytoma/paraganglioma. (PubMed, Endocr Connect) - "When rapid tumor control is needed, etoposide, doxorubicin, cisplatin, and mitotane remains the standard first-line regimen...Cyclophosphamide, vincristine, and dacarbazine may be considered for aggressive disease, rapid growth, or high tumor burden. Targeted and radiopharmaceutical approaches have expanded options, including high-specific-activity 131I-iobenguane for MIBG-avid tumors, 177Lu-DOTATATE for somatostatin receptor-positive disease, antiangiogenic tyrosine kinase inhibitors, and HIF-2α inhibition with belzutifan in selected molecular contexts. For both ACC and PPGL, controlling steroid or catecholamine excess is crucial, because endocrine complications affect treatment tolerance and outcomes. Future progress requires robust biomarkers, rational treatment sequencing, and trials using disease-specific endpoints beyond radiographic response and integrating patient-centered endocrine, molecular, and overall clinical measures of benefit."

IO biomarker • Journal • Adrenal Cortex Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • EPAS1 • SSTR

International Delphi-based Consensus: Therapeutic Approaches for Pediatric Adrenocortical Carcinoma. (PubMed, Eur J Endocrinol) - "These statements are intended to support clinicians in delivering more consistent and standardized therapeutic strategies for pediatric ACC. Future efforts should prioritize the design and conduct of high-quality, collaborative research studies in order to provide more evidence and therapy improvements."

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