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Chemotherapy for Early-stage High-risk Endometrial Cancer

European Oncology, 2009;5(1):71-3 DOI: http://doi.org/10.17925/EOH.2009.05.1.71

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, these patients have five-year overall survival of approximately 80%. In this group there is a need for an effective systemic adjuvant therapy. Mainly based on superior response rates, doxorubicin + cisplatin was for many years the standard chemotherapy in endometrial cancer. Gynecologic Oncology Group (GOG)-177 was the first phase III study on chemotherapy in endometrial cancer that showed a survival advantage. Paclitaxel + doxorubicine + cisplatin was better than doxorubicine + cisplatin, but the toxicity of the three-drug regimen has precluded general cceptance. Paclitaxel + carboplatin has produced high response rates and is widely used, despite the lack of evidence based on randomised studies. GOG-122 compared doxorubicine + cisplatin with whole abdominal radiotherapy in advanced optimally operated endometrial cancer and showed that chemotherapy with doxorubicine + cisplatin resulted in superior survival. Two recent studies have compared adjuvant chemotherapy (cyclophosphamide + doxorubicine + cisplatin) with adjuvant radiotherapy in early-stage endometrial cancer. Both studies failed to show a difference between the treatments. Another study (NSGO-EC-9501/EORTC-55991) compared adjuvant radiotherapy plus chemotherapy with adjuvant radiotherapy, and showed better survival with the sequential combination.

Endometrial cancer (EC) is the most common gynaecological cancer in the developed world, and in 2002 it was estimated that worldwide around 200,000 women were diagnosed with the disease.1 In Sweden, between 1970 and 2006 the age-standardised incidence increased by 37%, but because of an ageing population the number of cases increased by 80% during the same period.2 EC has a good prognosis, but per stage it is about the same as for ovarian cancer.3 In International Organization for Gynaecology and Obstetrics (FIGO) stage I there are subgroups with a high risk of micrometastatic disease. For example, patients with stage IC grade 3 disease have 79% five-year overall survival (OS) despite liberal use of adjuvant radiotherapy (RT).3 Four large trials have randomised patients to adjuvant pelvic RT or observation after surgery.4–7 All four failed to show an improvement in OS, despite the fact that RT prevented up to 80% of progressions in the irradiated field. Thus, most patients harbouring micrometastatic disease also have dissemination outside the irradiated field and there is a need for systemic adjuvant therapy, either added to or instead of RT.

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