title: ADH-1 in the treatment of metastatic adrenocortical carcinoma--case report.
abstract: 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 anti-vascular 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.
authors: The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada. Nirit.yarom@gmail.com
authors: Nirit
authors: N
authors: Yarom
authors: David
authors: D
authors: Stewart
authors: Leonard
authors: L
authors: Avruch
authors: Rajesh
authors: R
authors: Malik
authors: Julie
authors: J
authors: Wells
authors: Derek J
authors: DJ
authors: Jonker
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000473:pathology / Q000628:therapy*; D018268:Adrenocortical Carcinoma / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015820:Cadherins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D017321:Clinical Trials, Phase I as Topic; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D009842:Oligopeptides / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C518575:ADH-1 pepide; D015820:Cadherins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin