Adjuvant Chemotherapy in Endometrial Carcinoma: Overview of Randomised Trials

Abstract 

Endometrial cancer generally has a good prognosis because most cases are diagnosed in stage I. It is possible to identify subgroups of patients with early stage endometrial cancer with a poor prognosis. Despite a traditional generous use of adjuvant radiotherapy those patients have less than an 80% 5-year overall survival. In this group there is a need for an effective systemic adjuvant therapy. Two randomised studies have shown better response rates but no significant difference in overall survival for doxorubicin–cisplatin vs doxorubicin in advanced or recurrent endometrial cancer. Mainly on the basis of the superior response rates, doxorubicin–cisplatin was for many years regarded as the standard chemotherapy in endometrial cancer. GOG-177 was the first phase III study on chemotherapy in advanced or recurrent endometrial cancer that showed a survival advantage. Paclitaxel–doxorubicin–cisplatin was better than doxorubicin–cisplatin, but the toxicity of the three-drug regimen has precluded general acceptance. Paclitaxel–carboplatin has rendered high response rates in endometrial cancer and is widely used, despite the lack of evidence based on randomised studies. GOG-122 was a pivotal randomised study that compared doxorubicin–cisplatin with whole abdominal radiotherapy in advanced optimally operated endometrial cancer and showed that chemotherapy with doxorubicin–cisplatin resulted in superior survival. Two recent studies have compared adjuvant chemotherapy (cyclophosphamide–doxorubicin–cisplatin) with adjuvant radiotherapy in early stage endometrial cancer. Both studies failed to show a difference between the treatments, but neither was powered to show non-inferiority. Another study (NSGO-EC-9501/EORTC-55991) compared adjuvant radiotherapy plus chemotherapy with adjuvant radiotherapy and showed better survival with the combination. The implications of these studies are discussed.

Key words: Adjuvant, chemotherapy, endometrial, micrometastatic