Salvage Treatment of Adrenocortical Carcinoma with Trofosfamide

Kroiß, Matthias; Deutschbein, Timo; Schlötelburg, Wiebke; Ronchi, Cristina L.; Neu, Bruno; Müller, Hans‐Helge; Quinkler, Marcus; Hahner, Stefanie; Heidemeier, Anke; Fassnacht, Martin

doi:10.1007/s12672-016-0260-7

Cited by 16 publications

(10 citation statements)

References 41 publications

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“…However, as recently described in the FIRM-ACT trial, even the combination of mitotane with etoposide, doxorubicin and cisplatin (EDP) resulted in an overall survival of only 14.8 month in advanced ACC [ 21 ]. In addition, the results of other medical approaches are also of limited or no efficacy [ 22 – 27 ].…”

Section: Discussionmentioning

confidence: 99%

Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study

et al. 2017

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BackgroundMetastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC.MethodsA retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included.ResultsSeventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival.ConclusionsLiver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome.

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Section: Discussionmentioning

confidence: 99%

Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study

et al. 2017

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“…A total of 27 publications reported outcomes of 29 different systemic therapies for advanced or recurrent ACC (30,66,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125); two were randomized controlled trials ( (30,102); see Appendix 6 for details of studies included). The first randomized trial compared mitotane plus a combination of etoposide, doxorubicin and cisplatin (EDP-M) to mitotane plus streptozocin in 204 patients with advanced ACC (30).…”

Section: Question 4: Therapy For Advanced or Recurrent Diseasementioning

confidence: 99%

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors

Fassnacht

Dekkers

Else

et al. 2018

European Journal of Endocrinology

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658

867

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Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. Selected Recommendations: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting. (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete en bloc resection (including resection of oligo-metastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemoembolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients, we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.

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“…In a small study (n = 21), we could show disease stabilization with trofosfamid in 14 % of patients with a median PFS of 84 days and median OS of 198 days [36]. No objective response was seen in this cohort of heavily pretreated patients with a median number of three previous regimens.…”

Section: Trofosfamidementioning

confidence: 63%

Advanced Adrenocortical Carcinoma – What to do when First-Line Therapy Fails?

Megerle

Kroiß

Hahner

et al. 2018

Exp Clin Endocrinol Diabetes

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Adrenocortical carcinoma is a rare endocrine malignant disease with a generally unfavorable but heterogeneous prognosis. Although even in advanced stages a subset of patients experiences long-term disease stabilisation, effective systemic treatment options are limited. Mitotane is the only approved drug and the combination of etoposide, doxorubicin and cisplatin (plus mitotane) is currently considered as treatment standard for advanced adrenocortical carcinoma based on the results of a large randomized phase III trial. However, progression-free survival is often limited and further treatment options are frequently needed. Here we summarize the current knowledge about second and third-line therapeutic modalities (local and systemic) in advanced disease. Following the recent ESE-ENSAT guidelines local therapies play an important role for these patients. Regarding systemic therapies the best data are available for gemcitabine+capecitabine or streptozotocin (both with or without mitotane). Furthermore, we introduce our own approach to patients with advanced adrenocortical carcinoma based on our experience as a large multidisciplinary clinic dedicated to the care of patients with this orphan disease.

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Salvage Treatment of Adrenocortical Carcinoma with Trofosfamide

Cited by 16 publications

References 41 publications

Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study

Outcome after resection of Adrenocortical Carcinoma liver metastases: a retrospective study

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors

Advanced Adrenocortical Carcinoma – What to do when First-Line Therapy Fails?

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