Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies.
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.
Hogberg
Thomas
T
Department of Cancer Epidemiology, University of Lund, University Hospital, Lund, Sweden. thomas.hogberg@med.lu.se
Signorelli
Mauro
M
de Oliveira
Carlos Freire
CF
Fossati
Roldano
R
Lissoni
Andrea Alberto
AA
Sorbe
Bengt
B
Andersson
Håkan
H
Grenman
Seija
S
Lundgren
Caroline
C
Rosenberg
Per
P
Boman
Karin
K
Tholander
Bengt
B
Scambia
Giovanni
G
Reed
Nicholas
N
Cormio
Gennaro
G
Tognon
Germana
G
Clarke
Jackie
J
Sawicki
Tomasz
T
Zola
Paolo
P
Kristensen
Gunnar
G
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
D004317:Doxorubicin; D002945:Cisplatin