title: Combination chemotherapy in advanced adrenocortical carcinoma.
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.).
authors.affiliation: Department of Internal Medicine I, University Hospital, Würzburg, Germany. fassnacht_m@medizin.uni-wuerzburg.de
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
authors.forename: Harm
authors.initials: H
authors.lastname: Haak
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.forename: Staffan
authors.initials: S
authors.lastname: Welin
authors.forename: Carmen
authors.initials: C
authors.lastname: Schade-Brittinger
authors.forename: André
authors.initials: A
authors.lastname: Lacroix
authors.forename: Barbara
authors.initials: B
authors.lastname: Jarzab
authors.forename: Halfdan
authors.initials: H
authors.lastname: Sorbye
authors.forename: David J
authors.initials: DJ
authors.lastname: Torpy
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Stepan
authors.forename: David E
authors.initials: DE
authors.lastname: Schteingart
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.forename: Matthias
authors.initials: M
authors.lastname: Kroiss
authors.forename: Sophie
authors.initials: S
authors.lastname: Leboulleux
authors.forename: Paola
authors.initials: P
authors.lastname: Sperone
authors.forename: Anders
authors.initials: A
authors.lastname: Sundin
authors.forename: Ilse
authors.initials: I
authors.lastname: Hermsen
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.forename: Holger S
authors.initials: HS
authors.lastname: Willenberg
authors.forename: Antoine
authors.initials: A
authors.lastname: Tabarin
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.forename: Christelle
authors.initials: C
authors.lastname: de la Fouchardière
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Franco
authors.initials: F
authors.lastname: Mantero
authors.forename: Dirk
authors.initials: D
authors.lastname: Weismann
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Hanneke
authors.initials: H
authors.lastname: Wilmink
authors.forename: Monica
authors.initials: M
authors.lastname: Sender
authors.forename: Maureen
authors.initials: M
authors.lastname: Edgerly
authors.forename: Werner
authors.initials: W
authors.lastname: Kenn
authors.forename: Tito
authors.initials: T
authors.lastname: Fojo
authors.forename: Hans-Helge
authors.initials: HH
authors.lastname: Müller
authors.forename: Britt
authors.initials: B
authors.lastname: Skogseid
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy*; D018268:Adrenocortical Carcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D013311:Streptozocin; D005047:Etoposide; D008939:Mitotane; D004317:Doxorubicin; D002945:Cisplatin