Gemcitabine-Based Chemotherapy In Adrenocortical Carcinoma: A Multicentric Study On Efficacy and Predictive Factors.

Gemcitabine-Based Chemotherapy In Adrenocortical Carcinoma: A Multicentric Study On Efficacy and Predictive Factors.

J Clin Endocrinol Metab. 2017 Sep 19;:

Authors: Henning JEK, Deutschbein T, Altieri B, Steinhauer S, Kircher S, Sbiera S, Wild V, Schlötelburg W, Kroiss M, Perotti P, Rosenwald A, Berruti A, Fassnacht M, Ronchi CL

Abstract
Context: Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Beyond combination chemotherapy with cisplatin, etoposide, doxorubicin and mitotane, second/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, hENT1 and/or 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 multicentric study.
Setting: Referral centers of university hospitals.
Patients and materials: 145 patients with advanced ACC were treated with GEM-based chemotherapy (132 with concomitant capecitabine). FFPE tumor material was available for 70 patients for immunohistochemistry.
Outcome measures: Main outcome measures were progression-free survival (PFS) and objective response to GEM-based chemotherapy. Secondary objective was the predictive role of hENT1 and RRM1.
Results: Median PFS in the patient population was 12 weeks (range: 1-94). 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 grade 3 or 4 occurring in 11.0% of cases. No significant impact of hENT1 and/or RRM1 expression was observed on response to GEM-based chemotherapy.
Conclusions: GEM-based chemotherapy is a well-tolerated, but modestly active regimen in ACC patients with advanced disease. No reliable molecular predictive factors could be identified. Due to scarce alternative therapeutic options, GEM-based chemotherapy remains an important option for salvage treatment in advanced ACC.

PMID: 29092062 [PubMed - as supplied by publisher]

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