2 - Novel treatment strategies for targeting genetic changes in endometrial cancer

Summary

Introduction

Endometrial cancer is the most common gynaecological malignancy in Europe and the USA and the fourth most common cancer in women in the UK. In 2007, 7536 cases of endometrial cancer were diagnosed (approximately 5% of all female cancers) and 1741 deaths in 2008 were attributed to the disease, accounting for 2.3% of all deaths from malignancy in women. In the USA, approximately 42200 cases are diagnosed annually and 7780 deaths occur. The incidence of endometrial cancer increases with age and over 90% of women are diagnosed above the age of 50 years (median age 63 years). Most of these women (approximately 75%) are diagnosed at an early stage (stage I/II) and are potentially cured by surgery with or without adjuvant radiotherapy, resulting in a 5 year survival rate of 75—91%. However, the prognosis for women with recurrent or advanced endometrial cancer is poor, with a median overall survival of 9—10 months.

Current treatments for advanced endometrial cancer are chemotherapy or hormonal therapy. Doxorubicin, cisplatin, carboplatin, docetaxel, topotecan and paclitaxel have all shown activity as monotherapy, with response rates in the range 17—37%. Various combination regimens that include doxorubicin and/or a platinum have been investigated. However, randomised trials have failed to show any survival benefit of combinations of doxorubicin plus either cyclophosphamide or cisplatin compared with single-agent doxorubicin.