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Adrenocortical cancer: a therapeutic approach with everolimus (RAD001)

#66

Introduction: Adrenocortical cancer (ACC) is a rare disease with very poor outcome. ACC responds poorly to standard chemotherapy. Mitotane, used as adjuvant therapy to surgery, prolongs recurrence-free survival, but the response is limited to 23% of patients and resistance occurs in the majority of patients (1). There is no curative therapy for ACC. Pre-clinical studies have shown involvement of both IGF-2/IGF-1R and Akt/mTOR pathways in ACC, and IGF-1R and mTOR inhibitors inhibited cell proliferation of human adrenocortical carcinoma cell lines in vitro (2,3,4).

Aim(s): To evaluate the therapeutic effects of everolimus (RAD001, Novartis) in ACC.

Materials and methods: A female patient, diagnosed incidentally with a non-functioning right ACC, underwent laparoscopic resection. The histology confirmed malignancy. Referred to our department, the patient was started on mitotane. Two months later, she developed a single liver metastasis which was ablated with radiofrequency (RFA) six months after resection of the primary lesion. Subsequent imaging did not show new lesions or local recurrence. However, one year after resection of the primary lesion, she developed three new liver metastases and a large retroaortocaval lymph node. The patient refused standard chemotherapy. A low neutrophil count and raised gamma GT related to mitotane precluded entry to an experimental phase I clinical trial with an angiogenesis inhibitor. She received treatment instead with a selective IGF-1R inhibitor, OSI906 (OSI Pharmaceuticals Inc, NY) elsewhere (phase I trial, 150 mg twice daily), but showed progression and this was stopped. She was then treated with everolimus (RAD001) 10 mg daily.

Conference: 7th Annual ENETSConcerence (2010)

Presenting Author:

Authors: Gueorguiev M, Bhattacharya S, Grossman A,

Keywords: adrenocortical cancer, mTOR inhibitors, everolimus,

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