Endocrine Abstracts

Introduction: Malignant paraganglioma/pheochromocytoma (MPP) are very rare neuroendocrine tumors with heterogeneous prognostic and no gold-standard treatment. MPP can be associated with germline mutations at SDH-x genes which encode for the succinate dehydrogenase that catalyzes the oxidation of succinate to fumarate. SDH-x mutations lead to inactivation of the enzyme and thus accumulation of succinate.Aim: This project aims to evaluate...

Context: Mitotane due to its adrenolytic action is highly effective in long-term management of ACTH-dependent Cushing’s syndrome (CS). However, the slow onset of its anticortisolic effect makes its use problematic in severe CS, when very rapid therapeutic response is required. Association with metyrapone and ketoconazole, rapidly acting steroidogenesis inhibitors, could warrant CS control while waiting for the full efficiency of mitotane and thus avoid urgently performed ...

Introduction: Current medical treatment of adrenocortical carcinoma (ACC) is based on mitotane alone or in combination with cytotoxic chemotherapy. However, very little is known about the pharmacokinetic properties of mitotane and dosing schedules are based on clinical experience only. The aim of this study was to investigate the relationship between mitotane dose and plasma concentration comparing two pre-defined treatment regimens. Secondary objectives were to evaluate safet...

Background: No randomized trials have been conducted in adrenocortical carcinoma (ACC) patients. Treatment recommendations for this rare but aggressive disease have been based on data from small phase II trials. We have now performed the first randomized phase III trial, comparing etoposide, doxorubicin, cisplatin, plus mitotane (EDP-M) against streptozotocin plus mitotane (Sz-M).Methods: Three-hundred and four chemotherapy-naive patients with ACC not am...

Context: Peritoneal carcinomatosis (PC) is a rare site of distant metastasis in patients with adrenocortical cancer (ACC). One preliminary study suggests an increase risk of PC after adrenalectomy through laparoscopic approach of ACC.Objective: The objective of the study was to search for risk factors of PC including surgical approach. This was a retrospective cohort study conducted in an institutional practice.Patients: Sixty-four...

Introduction: The French National Institute of Cancer (INCa) launched supported by the Ministry of Health in 2008 a program for the recognition of national networks for the management of rare cancers. Among the 23 selected networks COMETE-Cancer was recognized by INCa in 2009 for Adrenocortical carcinoma (ACC) and malignant pheochromocytoma/paraganglioma (MPP). At that time 60–120 new ACC/year and 30 new MPP/year were expected at the national level....

Interferon-α (IFN-α) has shown some activity in neuroendocrine tumors with disease stabilizations. Malignant pheochromocytoma and paraganglioma (MPPGLs) have a heterogeneous behavior with a slow progression rate, most of the time and a high frequency of bone metastases. Stabilizing disease and preventing skeletal-related events are two goals to achieve in the management of MPPGLs patients.This retrospective study evaluated a multimodal strategy...

We have demonstrated that adjuvant mitotane prolong recurrence free survival (RFS) in patients with radically resected ACC. Aim of the present study was to correlate mitotane levels with patient outcome in an adjuvant setting in 3 different referral centres in Europe. There were 120 patients (45 W, 75 M, median age 44 years, range 16–76) radically resected for ACC who were treated adjuvantly with mitotane from 1996 to 2010. ACC was stage I in 10 cases, II in 73, III in 31...

Background: The benefit to risk ratio of mitotane high starting dose regimen in ACC remains unknown.Methods: To evaluate a high starting dose strategy, we performed a single-center, prospective study with three main objectives: 1) to assess the time taken to reach a mitotane plasma level above 14 mg/l (benefit); 2) to evaluate mitotane tolerance (risk) in the first 3 months of treatment and 3) to analyse the correlation using a regression analysis test b...

Introduction: O,p’DDD is the drug of choice for patients with adrenocortical carcinoma (ACC). Monitoring o,p’DDD serum level has been proposed as predictor of tumour response. Measurement of o,p’DDD metabolites involved in the active pathway may provide an improved prediction of o,p’DDD activity. The objective of our study was to (1)to confirm the currently used threshold o,p’DDD serum level of 14mg/l for achieving a tumour response and (2)compare the ...