Treatment of Advanced Adrenocortical Carcinoma with Erlotinib plus Gemcitabine

Quinkler, Marcus; Hahner, Stefanie; Wortmann, Sebastian; Johanssen, Sarah; Adam, Patrick; Ritte, Christian; Strasburger, Christian J.; Allolio, Bruno; Fassnacht, Martin

doi:10.1210/jc.2007-2564

Cited by 132 publications

(80 citation statements)

References 30 publications

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“…Our study confirms the disappointing results of salvage therapies in ACC reported in other studies (29,33,34). It further demonstrates that the natural course of ACC is progressive and that spontaneous tumour regressions as described for other tumour entities, e.g.…”

Section: Discussionsupporting

confidence: 89%

“…Etoposide, doxorubicin and cisplatin plus mitotane as well as streptozotocin plus mitotane were administered in all patients (nine of them within the FIRM-ACT trial). Furthermore, six patients were pretreated with gemcitabine plus erlotinib (29), three with sunitinib and three with radiotherapy and chemoembolization necessary. Five patients had concomitant mitotane, because it was at the discretion of the local physician to continue with mitotane when some clinical benefit was presumed.…”

Section: Patient Characteristicsmentioning

confidence: 99%

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Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma

Wortmann

Quinkler

Ritter

et al. 2010

European Journal of Endocrinology

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112

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Section: Discussionsupporting

confidence: 89%

Section: Patient Characteristicsmentioning

confidence: 99%

Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma

Wortmann

Quinkler

Ritter

et al. 2010

European Journal of Endocrinology

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112

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“…In 10 patients with advanced adrenocortical carcinoma, the combination of the EGFR inhibitor erlotinib with gemcitabine did not lead to any objective tumor response, and preliminary similar results were reported for gefitinib. 45,46 During our work-up all cases with no specific staining for EGFR on the TMAs were stained in sections from the corresponding original tissue blocks. Although a majority of cases (n ¼ 41; 63%) remained negative, focal expression of EGFR was observed in the other cases (weak n ¼ 7, moderate n ¼ 11 and strong n ¼ 6), demonstrating the known heterogeneous expression of EGFR that has also been described for other tumor entities.…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor in adrenocortical tumors: analysis of gene sequence, protein expression and correlation with clinical outcome

et al. 2010

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Adrenocortical carcinoma is a rare but highly malignant neoplasm with still limited treatment options. Epidermal growth factor receptor (EGFR) has been shown to be overexpressed in many solid tumors, but its expression in adrenocortical carcinoma has been studied only in a limited number of cases. Therefore, we analyzed the expression of EGFR in 169 adrenocortical carcinoma samples and compared it with 31 adrenocortical adenomas. Additionally, in 30 cases of adrenocortical carcinoma, exons 18-21 of the EGFR gene were cloned and sequenced. EGFR expression was found in 128 of 169 adrenocortical carcinoma samples (76%), and in 60 of these samples ( ¼ 36%) strong membrane staining was detected. However, there was no significant correlation with clinical outcome. In addition, all 30 sequenced cases revealed unmutated EGFR genes. In contrast, only 1 out of 31 adrenocortical adenomas weakly expressed the EGFR (3%). In summary, EGFR was overexpressed in more than three-quarters of adrenocortical carcinoma cases of this series. However, no mutations of the EGFR gene were found and EGFR expression was not of prognostic relevance. As EGFR is hardly expressed in adrenocortical adenomas, our results suggest that its expression in adrenocortical tumors indicates a malignant phenotype, which may be used in the differential diagnosis between adrenocortical adenomas and carcinomas.

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“…The efficacy of combined treatment with erlotinib and gemcitabine as salvage therapy was assessed in the group of patients with progressive ACC after two to four previous systemic therapies. Only one in 10 patients experienced a minor response, whereas eight patients progressed, suggesting that salvage chemotherapy using this regimen has no benefit in patients with very advanced ACC [180].…”

Section: Selected Targeted Therapies In Adrenocortical Cancermentioning

confidence: 99%

Szlaki molekularne w raku kory nadnercza — od wiedzy o sygnalizacji komórkowej do metod diagnostyki i leczenia

Szyszka

Grossman

Díaz‐Cano

et al. 2015

Endokrynologia Polska

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Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The prognosis is poor, and at diagnosis 30-40% of cases are already metastatic. The current therapeutic options (surgical resection, followed by adjuvant mitotane treatment +/-chemotherapy) are limited, and the results remain unsatisfactory. Key molecular events that contribute to formation of adrenocortical cancer are IGF2 overexpression, TP53-inactivating mutations, and constitutive activation of the Wnt/b-catenin signalling pathway via activating mutations of the b-catenin gene. The underlying genetic causes of inherited tumour syndromes have provided insights into molecular pathogenesis. The increased occurrence of adrenocortical tumours in Li-Fraumeni and Beckwith-Wiedemann syndromes, and Carney complex, has highlighted the roles of specific susceptibility genes: TP53, IGF2, and PRKAR1A, respectively. Further studies have confirmed that these genes are also involved in sporadic tumour cases. Crucially, transcriptome-wide studies have determined the differences between malignant and benign adrenocortical tumours, providing potential diagnostic tools. In conclusion, enhancing our understanding of the molecular events of adrenocortical tumourigenesis, especially with regard to the signalling pathways that may be disrupted, will greatly contribute to improving a range of available diagnostic, prognostic, and treatment approaches. StreszczenieRak kory nadnercza charakteryzuje się niską wyleczalnością i wysokim ryzykiem nawrotu. Rokowanie jest złe, a 30-40% przypadków okazuje się być przerzutami już przy diagnozie. Obecnie dostępne opcje terapeutyczne (chirurgiczna resekcja z następującym adjuwantowym leczeniem mitotanem, czasem połączonym z chemoterapią) są ograniczone, a ich wyniki są mało satysfakcjonujące. Kluczowe zmiany molekularne przyczyniające się to rozwoju raka kory nadnercza to nadekspresja IGF2, mutacje inaktywujące TP53 oraz konstytutywna aktywacja szklaku sygnałowego Wnt/b-katenina poprzez mutacje aktywujące gen b-kateniny. Genetyczne przyczyny leżące u podstaw dziedzicznych zespołów nowotworowych dostarczyły wgląd w ich patogenezę molekularną. Zespoły: Li-Fraumeni, Beckwitha-Wiedemanna oraz Carneya, charakteryzujące się zwiększoną predyspozycją do nowotworów kory nadnercza, uwidoczniły określone geny podatności, odpowiednio: TP53, IGF2 oraz PRKAR1A. Dalsze badania potwierdziły udział tych genów także w nowotworach sporadycznych. Co istotne, badania transkryptomu wykazały istotne różnice między nowotworami złośli-wymi i łagodnymi, dostarczając potencjalnych opcji diagnostycznych. Podsumowując, wzbogacenie wiedzy na temat molekularnych podstaw, a szczególnie szlaków sygnałowych, które mogą być zaburzone w procesie nowotworzenia w obrębie kory nadnercza znacznie przyczyni się poprawieniu możliwości diagnostycznych, rokowniczych oraz leczniczych. (Endokrynol Pol 2016; 67 (4): 427-440) Słowa kluczowe: rak kory nadnerczy; nowotwory kory nadnercza; patologia molekularna; szlaki transdukcji sygnałów; zespoły n...

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Treatment of Advanced Adrenocortical Carcinoma with Erlotinib plus Gemcitabine

Abstract: Salvage chemotherapy using erlotinib plus gemcitabine has very limited to no activity in patients with very advanced ACC.

Cited by 132 publications

References 30 publications

Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma

Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma

Epidermal growth factor receptor in adrenocortical tumors: analysis of gene sequence, protein expression and correlation with clinical outcome

Szlaki molekularne w raku kory nadnercza — od wiedzy o sygnalizacji komórkowej do metod diagnostyki i leczenia

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