title: Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies.
abstract: BACKGROUND
  Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled.
  
  
  METHODS
  Patients (n=540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy.
  
  
  RESULTS
  In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41-0.99; P=0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P=0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P=0.01).
  
  
  CONCLUSIONS
  Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.
authors.affiliation: Department of Cancer Epidemiology, University of Lund, University Hospital, Lund, Sweden. thomas.hogberg@med.lu.se
authors.forename: Thomas
authors.initials: T
authors.lastname: Hogberg
authors.forename: Mauro
authors.initials: M
authors.lastname: Signorelli
authors.forename: Carlos Freire
authors.initials: CF
authors.lastname: de Oliveira
authors.forename: Roldano
authors.initials: R
authors.lastname: Fossati
authors.forename: Andrea Alberto
authors.initials: AA
authors.lastname: Lissoni
authors.forename: Bengt
authors.initials: B
authors.lastname: Sorbe
authors.forename: Håkan
authors.initials: H
authors.lastname: Andersson
authors.forename: Seija
authors.initials: S
authors.lastname: Grenman
authors.forename: Caroline
authors.initials: C
authors.lastname: Lundgren
authors.forename: Per
authors.initials: P
authors.lastname: Rosenberg
authors.forename: Karin
authors.initials: K
authors.lastname: Boman
authors.forename: Bengt
authors.initials: B
authors.lastname: Tholander
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Nicholas
authors.initials: N
authors.lastname: Reed
authors.forename: Gennaro
authors.initials: G
authors.lastname: Cormio
authors.forename: Germana
authors.initials: G
authors.lastname: Tognon
authors.forename: Jackie
authors.initials: J
authors.lastname: Clarke
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sawicki
authors.forename: Paolo
authors.initials: P
authors.lastname: Zola
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kristensen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant / Q000379:methods; D016019:Survival Analysis
chemical_list: D004317:Doxorubicin; D002945:Cisplatin