ADH-1 in the treatment of metastatic adrenocortical carcinoma - Case report

Nirit Yarom*, David Stewart, Leonard Avruch, Rajesh Malik, Julie Wells, Derek J. Jonker

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Adrenocortical Carcinoma (ACC) is rare with an annual incidence of 0.5-2 cases per million worldwide. Some ACC tumors over express N-cadherin, which correlates with metastatic potential. ADH-1 (Exherin™) is a competitive inhibitor of N-cadherin, resulting in rapid onset of tumor vascular angiolysis and apoptosis in preclinical models. Targeting N-cadherin may cause direct anti-tumor and antivascular effects. We report a case of ACC with benefit from ADH-1 therapy. A 24 year old woman with an N-cadherin expressing metastatic ACC was treated on a phase I trial and treated with ADH-1 subsequently received additional doses through a special access program. The patient presented with cushingoid features from cortisol over-secretion and was diagnosed with metastatic ACC in January 2003. Tumor progression followed treatment with a combination of doxorubicin, cisplatin and mitotane. In October 2003, as a part of a phase I clinical trial she was treated with as a single dose of ADH-1 at 150 mg/m 2. This resulted in transient normalization of Cortisol, tumor necrosis on CT imaging, and reduction in tumor perfusion on DCE-MRI. Following progression on several additional lines of chemotherapy, she was again treated with ADH-1 under a Special Access Program (SAP). After 33 weekly doses (22 with 150 mg/m 2 and 11 with 300 mg/m 2) radiographic tumor progression was demonstrated and treatment discontinued. She survived 40 months with metastatic disease, dying 12 months after her last dose of ADH-1. This observation merits consideration for prospectively evaluating the efficacy of ADH-1 in patients with cortisol secreting ACC that over express N-cadherin.

Original languageEnglish
Pages (from-to)3921-3925
Number of pages5
JournalAnticancer Research
Issue number11
StatePublished - Nov 2011
Externally publishedYes


  • ADH-1
  • Adrenocortical carcinoma
  • Dynamic contrast enhancing magnetic resonance imaging (DCE-MRI)
  • N-cadherin
  • Phase-I


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