Judith E K Henning1, Timo Deutschbein1, Barbara Altieri1,2, Sonja Steinhauer1, Stefan Kircher3,4, Silviu Sbiera1, Vanessa Wild3, Wiebke Schlötelburg5, Matthias Kroiss4, Paola Perotti6, Andreas Rosenwald3,4, Alfredo Berruti7, Martin Fassnacht1,4, Cristina L Ronchi1. 1. Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Wuerzburg, Wuerzburg 97070, Germany. 2. Division of Endocrinology and Metabolic Diseases, Catholic University of the Sacred Heart, Rome 00168, Italy. 3. Institute of Pathology, University of Wuerzburg, Wuerzburg 97070, Germany. 4. Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg 97070, Germany. 5. Institute for Diagnostic and Interventional Radiology, University Hospital of Wuerzburg, Wuerzburg 97070, Germany. 6. Division of Internal Medicine I, University of Turin, San Luigi Hospital, Turin 10124, Italy. 7. Division of Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Spedali Civili Hospital, Brescia 25151, Italy.
Abstract
Context: Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM. Objective: To assess the efficacy of GEM-based chemotherapy in ACC in a real-world setting and the predictive role of molecular parameters. Design: Retrospective multicenter study. Setting: Referral centers of university hospitals. Patients and Materials: A total of 145 patients with advanced ACC were treated with GEM-based chemotherapy (132 with concomitant capecitabine). Formalin-fixed paraffin-embedded tumor material was available for 70 patients for immunohistochemistry. Outcome Measures: The main outcome measures were progression-free survival (PFS) and an objective response to GEM-based chemotherapy. The secondary objective was the predictive role of hENT1 and RRM1. Results: The median PFS for the patient population was 12 weeks (range, 1 to 94). A partial response or stable disease was achieved in 4.9% and 25.0% of cases, with a median duration of 26.8 weeks. Treatment was generally well tolerated, with adverse events of grade 3 or 4 occurring in 11.0% of cases. No substantial effect of hENT1 and/or RRM1 expression was observed in response to GEM-based chemotherapy. Conclusions: GEM-based chemotherapy is a well-tolerated, but modestly active, regimen against advanced ACC. No reliable molecular predictive factors could be identified. Owing to the scarce alternative therapeutic options, GEM-based chemotherapy remains an important option for salvage treatment for advanced ACC.
Context:Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM. Objective: To assess the efficacy of GEM-based chemotherapy in ACC in a real-world setting and the predictive role of molecular parameters. Design: Retrospective multicenter study. Setting: Referral centers of university hospitals. Patients and Materials: A total of 145 patients with advanced ACC were treated with GEM-based chemotherapy (132 with concomitant capecitabine). Formalin-fixed paraffin-embedded tumor material was available for 70 patients for immunohistochemistry. Outcome Measures: The main outcome measures were progression-free survival (PFS) and an objective response to GEM-based chemotherapy. The secondary objective was the predictive role of hENT1 and RRM1. Results: The median PFS for the patient population was 12 weeks (range, 1 to 94). A partial response or stable disease was achieved in 4.9% and 25.0% of cases, with a median duration of 26.8 weeks. Treatment was generally well tolerated, with adverse events of grade 3 or 4 occurring in 11.0% of cases. No substantial effect of hENT1 and/or RRM1 expression was observed in response to GEM-based chemotherapy. Conclusions: GEM-based chemotherapy is a well-tolerated, but modestly active, regimen against advanced ACC. No reliable molecular predictive factors could be identified. Owing to the scarce alternative therapeutic options, GEM-based chemotherapy remains an important option for salvage treatment for advanced ACC.
Authors: Dwight H Owen; Sandipkumar Patel; Lai Wei; John E Phay; Lawrence A Shirley; Lawrence S Kirschner; Carl Schmidt; Sherif Abdel-Misih; Pamela Brock; Manisha H Shah; Bhavana Konda Journal: Horm Cancer Date: 2019-08-29 Impact factor: 3.869
Authors: Luigi Lorini; Salvatore Grisanti; Roberta Ambrosini; Deborah Cosentini; Marta Laganà; Luigi Grazioli; Guido A M Tiberio; Sandra Sigala; Alfredo Berruti Journal: Endocrine Date: 2019-09-06 Impact factor: 3.633
Authors: Matthias Kroiss; Felix Megerle; Max Kurlbaum; Sebastian Zimmermann; Julia Wendler; Camilo Jimenez; Constantin Lapa; Marcus Quinkler; Oliver Scherf-Clavel; Mouhammed Amir Habra; Martin Fassnacht Journal: J Clin Endocrinol Metab Date: 2020-05-01 Impact factor: 5.958