TY - JOUR
T1 - Combination chemotherapy in advanced adrenocortical carcinoma
AU - Fassnacht, Martin
AU - Terzolo, Massimo
AU - Allolio, Bruno
AU - Baudin, Eric
AU - Haak, Harm
AU - Berruti, Alfredo
AU - Welin, Staffan
AU - Schade-Brittinger, Carmen
AU - Lacroix, André
AU - Jarzab, Barbara
AU - Sorbye, Halfdan
AU - Torpy, David J.
AU - Stepan, Vinzenz
AU - Schteingart, David E.
AU - Arlt, Wiebke
AU - Kroiss, Matthias
AU - Leboulleux, Sophie
AU - Sperone, Paola
AU - Sundin, Anders
AU - Hermsen, Ilse
AU - Hahner, Stefanie
AU - Willenberg, Holger S.
AU - Tabarin, Antoine
AU - Quinkler, Marcus
AU - De La Fouchardière, Christelle
AU - Schlumberger, Martin
AU - Mantero, Franco
AU - Weismann, Dirk
AU - Beuschlein, Felix
AU - Gelderblom, Hans
AU - Wilmink, Hanneke
AU - Sender, Monica
AU - Edgerly, Maureen
AU - Kenn, Werner
AU - Fojo, Tito
AU - Müller, Hans Helge
AU - Skogseid, Britt
PY - 2012/6/7
Y1 - 2012/6/7
N2 - 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.)
AB - 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.)
UR - http://www.scopus.com/inward/record.url?scp=84861888600&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1200966
DO - 10.1056/NEJMoa1200966
M3 - Article
AN - SCOPUS:84861888600
SN - 0028-4793
VL - 366
SP - 2189
EP - 2197
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 23
ER -