Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer–Results from two randomised studies

Hogberg, Thomas; Signorelli, Mauro; de Oliveira, Carlos Freire; Fossati, Roldano; Lissoni, Andrea Alberto; Sorbe, Bengt; Andersson, Håkan; Grenman, Seija; Lundgren, Caroline; Rosenberg, Per; Boman, Karin; Tholander, Bengt; Scambia, Giovanni; Reed, Nicholas; Cormio, Gennaro; Tognon, Germana; Clarke, Jackie; Sawicki, Tomasz; Zola, Paolo; Kristensen, Gunnar

doi:10.1016/j.ejca.2010.06.002

« Previous Next »European Journal of Cancer
Volume 46, Issue 13 , Pages 2422-2431, September 2010

Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer–Results from two randomised studies

Thomas Hogberg
- Department of Cancer Epidemiology, University of Lund, University Hospital, SE-221 85 Lund, Sweden
- Corresponding author: Tel.: +46 46 177550; fax: +46 46 188143.
Mauro Signorelli
- Department of Obstetrics and Gynaecology, A. Manzoni Hospital, Lecco, Italy
Carlos Freire de Oliveira
- Department of Gynaecology, University Hospital, Coimbra, Portugal
Roldano Fossati
- Department of Oncology, Mario Negri Institute, Milan, Italy
Andrea Alberto Lissoni
- Department of Gynaecology and Obstetrics, S. Gerardo Hospital, Monza, Italy
Bengt Sorbe
- Department of Gynaecological Oncology, University Hospital, Örebro, Sweden
Håkan Andersson
- Department of Gynaecological Oncology, University Hospital, Gothenburg, Sweden
Seija Grenman
- Department of Obstetrics and Gynaecology, University Hospital, Turku, Finland
Caroline Lundgren
- Department of Gynaecological Oncology, Radiumhemmet, Karolinska Hospital Solna, Stockholm, Sweden
Per Rosenberg
- Department of Gynaecological Oncology, University Hospital, Linköping, Sweden
Karin Boman
- Department of Gynaecological Oncology, University Hospital, Umeå, Sweden
Bengt Tholander
- Department of Oncology, University Hospital, Uppsala, Sweden
Giovanni Scambia
- Department of Obstetrics and Gynaecology, Gemelli Hospital, Rome, Italy
Nicholas Reed
- Beatson Oncology Centre, Western Infirmary, Glasgow, UK
Gennaro Cormio
- Department of Obstetrics and Gynaecology, University of Bari, Bari, Italy
Germana Tognon
- Department of Obstetrics and Gynaecology, Spedali Civili, Brescia, Italy
Jackie Clarke
- Belfast City Hospital, Belfast, UK
Tomasz Sawicki
- Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland
Paolo Zola
- Department of Obstetrics and Gynaecology, Mauriziano Hospital, Turin, Italy
Gunnar Kristensen
- Department of Gynaecological Oncology and Institute of Medical Informatics, The Norwegian Radium Hospital, Oslo, Norway

Received 21 April 2010; received in revised form 26 May 2010; accepted 2 June 2010. published online 09 July 2010.

Abstract

Introduction

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).

Conclusion

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.

Keywords: Adjuvant therapy, Chemotherapy, Radiotherapy, Chemoradiotherapy, Endometrial cancer, Randomised clinical trial