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Combination chemotherapy in advanced adrenocortical carcinoma
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2012 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 366, no 23, 2189-2197 p.Article in journal (Refereed) Published
Abstract [en]


Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment.


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.


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.


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.

Place, publisher, year, edition, pages
2012. Vol. 366, no 23, 2189-2197 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-175725DOI: 10.1056/NEJMoa1200966ISI: 000304863400008PubMedID: 22551107OAI: oai:DiVA.org:uu-175725DiVA: diva2:532705
Available from: 2012-06-12 Created: 2012-06-12 Last updated: 2014-09-08Bibliographically approved

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Welin, StaffanSundin, AndersSkogseid, Britt
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