Lysodren (mitotane)

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.

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.

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.

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.

P=N/A, N=400, Active, not recruiting, University of Wuerzburg | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2025

Following surgery and adjuvant mitotane therapy, the patient showed no recurrence at a 5-year follow-up...This case was the first case report of myxoid ACC with a 1p deletion, which was reported to be detected in 67% of ACC and 9% of adenoma but not in hyperplasia, supporting the correlation of this aberration with tumorigenesis. In conclusion, 1p deletion may be relevant to tumorigenesis in myxoid ACC.

Mitotane, the medication licenced for ACC, has had mixed results...Paclitaxel and cisplatin were the central nodes within the drug-gene network...Network analysis shows fluorouracil and epirubicin target the ACC novel hub gene, HMMR. Fluorouracil was more effective due to its impact on M2 macrophage infiltration.

First-line mitotane therapy failed due to toxicity and progressive disease. We report a patient with metastatic adrenocortical carcinoma in Lynch syndrome who demonstrated an excellent response to pembrolizumab. Genetic analyses can play a beneficial role in cases of adrenocortical carcinoma.

Mitotane increases GDF-15 levels and is associated with poor response to ICI. GDF-15 may mediate reduced infiltration with immune cells in ACC.

P2, N=3, Terminated, M.D. Anderson Cancer Center | Completed --> Terminated; Slow accrual

P3, N=240, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2029 | Trial primary completion date: Jan 2025 --> Jan 2029

P2, N=28, Recruiting, West China Hospital | Trial completion date: Dec 2030 --> Dec 2031