Gemcitabine-Based Chemotherapy in Adrenocortical Carcinoma: A Multicenter Study of Efficacy and Predictive Factors

Judith E. K. Henning, Timo Deutschbein, Barbara Altieri, Sonja Steinhauer, Stefan Kircher, Silviu Sbiera, Vanessa Wild, Wiebke Schlötelburg, Matthias Kroiss, Paola Perotti, Andreas Rosenwald, Alfredo Berruti, Martin Fassnacht, Cristina Ronchi

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)4323-4332
JournalJournal of Clinical Endocrinology and Metabolism
DOIs
Publication statusPublished - 1 Nov 2017

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