Tamoxifen, a nonsteroidal antiestrogen with some estrogenic properties, was evaluated for treatment of metastatic endometrial carcinoma based on experience in using this agent in breast cancer treatment. Its use as either a single agent or in combination with a progestin is related to its ability to inhibit the binding of estradiol to the estrogen receptor and to increase progesterone-receptor expression. In a review of eight studies using tamoxifen, 20 to 40 mg per day, in patients with metastatic endometrial carcinoma, the overall response rate was 22%, with a range of 0% to 53% (365). Responses to tamoxifen were more likely to be observed in patients with low-grade, hormone receptor–positive tumors who had a prior response to progestin therapy. In an attempt to reverse the hormone receptor down-regulation seen with progestin therapy, tamoxifen was given along with progestins, but the overall responses to combined tamoxifen and progestin therapy were similar to those noted for single-agent progestin therapy.
Progestins are recommended as initial treatment for all patients with recurrent endometrioid tumors with hormone receptor–positive tumors. Radiation therapy, surgery, or both should be used whenever feasible for treatment of localized recurrent cancer such as vaginal, pelvic, bone, and peripheral lymph node disease; however, these patients should also be given longterm progestin therapy unless they are known to have a progesterone-receptor–negative tumor. Patients with nonlocalized recurrent tumors, especially if progesterone receptors are known to be positive, are candidates for progestin therapy, either megestrol acetate, 80 mg twice daily, or medroxyprogesterone acetate, 50 to 100 mg three times daily. Progestin therapy should be continued for at least 2 to 3 months before assessing response. If a response is obtained, the progestin should be continued for as long as the disease is static or in remission. In the presence of a relative contraindication to high-dose progestin therapy (e.g., prior or current thromboembolic disease, severe heart disease, or inability of the patient to tolerate progestin therapy), tamoxifen, 20 mg twice daily, is recommended. Failure to respond to hormonal therapy is an indication for initiating chemotherapy.
Chemotherapy Several chemotherapeutic agents or combinations of agents are capable of inducing objective responses and even remissions in patients with metastatic endometrial carcinoma, but all cytotoxic therapy should be considered palliative because response and survival times are short (365–368). The most active chemotherapeutic agents are doxorubicin, the platinum compounds cisplatin and carboplatin, and paclitaxel (Taxol). Doxorubicin, 50 to 60 mg/m2 every 3 weeks (366–368); cisplatin, 60 to 75 mg/m2 every 3 weeks; and carboplatin, 350 to 400 mg/m2 every 4 weeks are associated with response rates of 21% to 29%. Paclitaxel, 250 mg/m2 as a 24-hour infusion with granulocyte colony-stimulating factor support, or 175 mg/m2 as a 3-hour infusion every 3 weeks, produced response rates of about 36% (369–371). Alkylating agents such as cyclophosphamide and melphalan, 5-ﬂuorouracil, altretamine (hexamethylmelamine), liposomal doxorubicin, and topotecan show activity against endometrial cancer (371–374). Most responses obtained with use of these agents were partial, averaging only 3 to 6 months, with the median survival time ranging from 4 to 8 months.