Although the prognosis for women with endometrial cancer confined to the uterus is relatively good, with a 5-year survival of approximately 90%, women with advanced or recurrent disease have a much poorer outcome. Systemic hormonal therapy with progestins improves survival in progesterone-receptor-positive tumors but chemotherapy is indicated as front-line therapy for most patients with this disease. Few single chemotherapy agents achieve response rates greater than 20%. The combination of doxorubicin and cisplatin is the first-line treatment of choice but the response and survival rates are still low compared to ovarian cancer treatments and more active regimens are needed. Treatment options for second-line chemotherapy are even more limited because of low response rates and toxicity issues related to prior radiation therapy. The topoisomerase I inhibitor, topotecan, is being investigated for the treatment of endometrial cancer. In previously treated patients, single-agent topotecan achieved a response in 10% of patients and disease stabilized in 55% of patients. The combination of topotecan and cisplatin is being studied in chemotherapy-naive elderly patients. Topotecan is also active in uterine papillary serous carcinoma, an aggressive form of the disease that generally does not respond to chemotherapy. (C) 2003 Elsevier Inc. All rights reserved.