The Journal of clinical endocrinology and metabolism · 2017
Gemcitabine-Based Chemotherapy in Adrenocortical Carcinoma: A Multicenter Study of Efficacy and Predictive Factors.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Henning Judith E K, Deutschbein Timo, Altieri Barbara, Steinhauer Sonja, Kircher Stefan, Sbiera Silviu, Wild Vanessa, Schlötelburg Wiebke, Kroiss Matthias, Perotti Paola, Rosenwald Andreas, Berruti Alfredo, Fassnacht Martin, Ronchi Cristina L
Аннотация
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.
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.