ANTI-TUMOUR TREATMENTSystemic therapy in metastatic or recurrent endometrial cancer
Introduction
Endometrial carcinoma is the most common gynecological cancer, having an incidence in western countries of 15–20 per 100000 women per year.1 The American Cancer Society estimated that there were 40800 new cases of endometrial carcinoma and 7310 deaths in the United Stages in 2005.2 Endometrial carcinoma is the fourth most common cancer in females with approximately 7000 deaths each year, making it the 7th leading cause of death from malignancy in women. It is a disease of postmenopausal women, although 25% of the cases occur in premenopausal patients, with 5% occurring in patients younger than 40 years of age.3
At presentation, 75% of cases are stage I and an additional 13% are stage II. Most patients with stage I or II achieve cure with surgical resection or radiotherapy or a combination of two.4 Radiation, the standard modality along with surgery, for treatment of early disease5, 6, 7, 8 and local or regional recurrences,9 has no clear benefit in advanced stage patients or patients with non-localized recurrent disease.10, 11, 12 Chemotherapy and/or hormonal therapy are often considered to be the only active treatments in advanced disease.13 Many different chemotherapy and hormonal therapy agents have been tested in this setting. The most common regimens in clinical practice include doxorubicin (ADR), cisplatin (CDDP) and paclitaxel (Tx) (either as single agents or in combination), and progestins (megestrol acetate, medroxyprogesterone (MPA)).13 Response rates (RRs) to systemic therapy reported in the literature vary considerable, ranging from 10% to 78%, due to marked differences in the studied patient populations.14 Reported median survival times in patients with advanced or recurrent disease treated with chemotherapy is rarely more than 1 year. The activity of hormonal regimens, mainly progestins, is thought to be influenced by certain prognostic factors, such as receptor content.15 However, RRs are unlikely to be high and the exact impact on survival is uncertain.15, 16, 17 Several phase I and II trials have been conducted to evaluate the efficacy of the most commonly used regimens either as single agents18 or as combinations19, 20, 21, 22, 23 in an effort to identify better treatments.
This review was conducted in an attempt to evaluate the chemotherapeutic and hormonal therapy options for women with advanced or recurrent adenocarcinoma of the endometrium.
Section snippets
Prognostic factors
Surgical stage is strongly prognostic factor of the outcome for women with endometrial adenocarcinoma.24, 25, 26, 27, 28 Patients with stage I have 5-year survival rate of 88% compared with 55% for those with stage III.29 Histology has been recognized as being important in predicting survival in patients with endometrial carcinoma. Women with tumors of serous histology have a poor 5-year survival rate compared with that for tumors of endometrioid histology.30, 31, 32 This is related in large
Treatment
Once endometrial carcinoma is diagnosed, the treatment is total abdominal hysterectomy, bilateral salpingo-oophorectomy, with pelvic and/or para-aortic lymph nodes and peritoneal washings assessment with or without pelvic radiotherapy. The use of external pelvic radiotherapy for patients with poor prognosis disease is an accepted standard of care to decrease the risk of recurrent pelvic disease. Patients with recurrent endometrial cancer may be treated, depending on the sites of the recurrence
Endocrine therapy
Hormonal agents have been evaluated in patients with advanced or recurrent endometrial carcinoma. Since many patients with advanced or recurrent endometrial carcinoma present at an advanced age with other co-morbidities, endocrine therapy may be a therapeutic alternative for those with well-differentiated tumors or a long disease-free interval. In the 1970s, both parenteral and oral progestins yielded similar serum levels and RRs, which ranged from 18% to 34% in patients with advanced or
Chemotherapy
Chemotherapy has typically been reserved for patients with disseminated primary or recurrent disease. Several single agents and combination chemotherapy regimens have been evaluated in advanced or recurrent endometrial cancer. Chemotherapy is capable of inducing overall survival <12 months in patients with metastatic uterine cancer. In patients with recurrent disease responses to treatment are in the majority of cases partial, ranging 3–6 months, the time to tumor progression 4–6 months and the
Molecularly targeted therapy
Novel molecularly targeted therapies are currently under evaluation in endometrial carcinoma and in uterine serous papillary carcinoma (Table 5).
Recently, it has been shown that uterine serous papillary carcinoma (USPC) overexpresses HER-2/neu in 60–80% of the tested samples.110, 111 Uterine papillary serous carcinoma has similar histological findings but a more aggressive biological behaviour with respect to high-grade serous epithelial ovarian cancer (EOC). HER-2/neu is the most overexpressed
Conclusions
Progestins and combination chemotherapy are the most commonly used therapies for women with advanced or recurrent endometrial cancer. Patients with long disease-free interval, not candidates for chemotherapy and well differentiated or progesterone positive tumors should be treated with endocrine therapy (progestins). Systemic chemotherapy should be used in patients with rapidly progressive disease, poorly differentiated tumors and serous papillary and clear cell histology. Systemic chemotherapy
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