Lysodren (mitotane) / Perrigo Company - LARVOL DELTA

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

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

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

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

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

Establishment of a patient-derived adrenocortical carcinoma 3D tumor construct platform for evaluation of therapeutic strategies. (PubMed, bioRxiv) - "We then demonstrate the utility of ACC PTCs for evaluation of chemotherapies currently used clinically (mitotane) with and without experimental cocktails of etoposide, doxorubicin, and cisplatin, experimental targeted therapies, and cellular immunotherapies, primarily in the form of natural killer (NK) cell therapy. In particular, the latter - cellular immunotherapies - are cutting edge studies demonstrating potential to evaluate immunotherapies in ACC clinical scenarios. Together these data provide evidence that patient-derived ACC models can serve as an important tool for identification of future points of intervention and testing of novel therapeutic strategies to improve ACC clinical care."

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

Chemo-immunotherapy with cisplatin and nivolumab as second line approach in metastatic adrenocortical carcinoma. (PubMed, Eur J Endocrinol) - "Cisplatin and nivolumab is an active regimen in advanced, previously treated, ACC patients. The long survival achieved in this patient population with a poor prognosis is promising."

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

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

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

Mitotane dosage, plasma levels, and anthropometric measurements in pediatric adrenocortical carcinoma. (PubMed, Endocr Oncol) - "No significant differences in daily dose levels (mg/kg/day and mg/m2/day) were observed based on body weight. This study supports estimating mitotane dosages in pediatric ACC, emphasizing the need for close monitoring and frequent follow-ups at specialized centers due to individualized dosing and a narrow therapeutic window."

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

Update and practical recommendations for the use of medical treatment of Cushing´s syndrome. (PubMed, Endocr Rev) - "Currently available medical treatments include adrenal steroidogenesis inhibitors that block cortisol secretion (ketoconazole, levoketoconazole, metyrapone, osilodrostat, mitotane, and etomidate), drugs that modulate pituitary ACTH secretion (pasireotide and cabergoline), and drugs that block peripheral glucocorticoid receptors (mifepristone). In this review, we summarize the main indications for medical treatment in CS, the mechanism of drug action, efficacy, recommended doses, and safety of the currently available drugs, as well as potential future treatments. We also discuss titration and block-and-replace approaches for control of hypercortisolism and provide recommendations for the use and monitoring of medical treatment in CS, including patients with endogenous hypercortisolism in special situations such as pregnancy, cyclic CS and mild autonomous cortisol secretion."

Journal • Cushing’s Disease • Endocrine Disorders

Adrenocortical Carcinoma and Inferior Vena Cava Thrombosis: Diagnosis and Perioperative Management. (PubMed, Cureus) - "This case reinforces the need for improved guidelines and increased education, accounting for the variable presentations of ACC, to enhance diagnostic accuracy and optimize pre- and perioperative planning. As such, in cases of patients presenting with masses in the adrenal-adjacent regions, an endocrine workup of cortisol, androgens/estrogens, and mineralocorticoids should be the standard of care to rule out aggressive tumors such as ACC."

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

Adrenocortical Mitochondria-Associated Membranes: Isolation, Characterization, and Lipidoproteomic Response to Mitotane. (PubMed, J Endocr Soc) - "MAMs were isolated from NCI-H295S cells treated with mitotane, the ferroptosis inducer RSL3, or control. In conclusion, locally reduced Q10 in MAM may contribute to impaired respiratory chain activity and free radical excess induced by mitotane. Recruitment of GRIPAP1 protein to MAMs may transduce cell death."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • ACSL4 • EIF2AK3 • ERN1 • PERK

The Intricate Puzzle of Adrenocortical Tumors: Revisitation of Two Old Cases of Virilizing Adrenocortical Neoplasia with Contradictory Diagnostic and Histopathological Findings and Opposite Conclusions. (PubMed, Life (Basel)) - "Mitotane treatment temporarily improved her condition, but it progressively worsened until her death 11 months later. The girl instead showed progressive improvement in clinical and laboratory findings until complete normalization in 18 months. The use of dated radiological and laboratory investigations suggests caution against generalization of our assumption; however, these cases suggest that only histopathological findings from surgical specimens ensure a correct diagnosis of adrenocortical masses."

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

Mitotane-Induced Hypothyroidism and Dyslipidemia in Adrenocortical Carcinoma: Sex Differences and Novel Evidence from a Thyroid Cell Model. (PubMed, Curr Oncol) - "These findings reveal sex-specific susceptibilities to mitotane toxicity and provide novel evidence of direct mitotane-induced thyroid cell damage. This insight supports the need for careful thyroid and lipid profile monitoring during mitotane treatment and may inform the development of safer therapies for ACC."

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

Impact of Adjuvant Radiotherapy and Mitotane on Survival in Localized Adrenocortical Carcinoma: A Retrospective Cohort Study. (PubMed, Int J Urol) - "Adjuvant RT achieves excellent LC with minimal toxicity in high-risk localized ACC. These exploratory findings, limited by small cohort size, retrospective design, and absence of a comparator group, warrant confirmation in larger prospective multicenter studies."

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

VLDL: The key factors influencing the distribution of mitotane in patients with adrenocortical carcinoma. (PubMed, J Pharm Anal) - "Image 1."

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

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