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Fassnacht, M; Terzolo, M; Allolio, B; Baudin, E; Haak, H; Berruti, A; Welin, S; Schade-Brittinger, C; Lacroix, A; Jarzab, B; Sorbye, H; Torpy, DJ; Stepan, V; Schteingart, DE; Arlt, W; Kroiss, M; Leboulleux, S; Sperone, P; Sundin, A; Hermsen, I; Hahner, S; Willenberg, HS; Tabarin, A; Quinkler, M; de la Fouchardire, C; Schlumberger, M; Mantero, F; Weismann, D; Beuschlein, F; Gelderblom, H; Wilmink, H; Sender, M; Edgerly, M; Kenn, W; Fojo, T; Müller, HH; Skogseid, B; FIRM-ACT Study Group.
Combination chemotherapy in advanced adrenocortical carcinoma.
N Engl J Med. 2012; 366(23):2189-2197
Doi: 10.1056/NEJMoa1200966
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- Co-Autor*innen der Med Uni Graz
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Stepan Vinzenz
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- Abstract:
- BACKGROUND Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment. METHODS We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival. RESULTS For first-line therapy, patients in the EDP-mitotane group had a significantly higher response rate than those in the streptozocin-mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P=0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP-mitotane group and 2.2 months in the streptozocin-mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments. CONCLUSIONS Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival. (Funded by the Swedish Research Council and others; FIRM-ACT ClinicalTrials.gov number, NCT00094497.)
- Find related publications in this database (using NLM MeSH Indexing)
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Adrenal Cortex Neoplasms - drug therapy
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Adrenocortical Carcinoma - drug therapy
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Adult -
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Aged -
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Antineoplastic Combined Chemotherapy Protocols - adverse effects
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Cisplatin - administration & dosage
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Disease-Free Survival -
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Doxorubicin - administration & dosage
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Etoposide - administration & dosage
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Female -
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Humans -
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Intention to Treat Analysis -
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Kaplan-Meier Estimate -
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Male -
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Middle Aged -
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Mitotane - administration & dosage
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Quality of Life -
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Streptozocin - administration & dosage
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Young Adult -