therapy attempted to reduce the risk of recurrence. This therapy is attractive because it provides systemic treatment and has few side effects. Unfortunately, several large randomized, placebo-controlled studies failed to identify a benefit for adjuvant progestin therapy (308–313).
Chemotherapy Adjuvant cytotoxic chemotherapy was studied in a few trials. The GOG treated 181 patients who had poor prognostic factors with postoperative radiation and then randomly assigned patients to receive no further therapy or doxorubicin chemotherapy. After 5 years of observation, there was no difference in recurrence rates between the two groups (314).
In cases of advanced disease, chemotherapy is now standard treatment. The GOG122 trial compared whole-abdominal radiotherapy versus systemic chemotherapy (eightcycles of doxorubicin and cisplatin) in 388 patients with stage III or IV disease who underwent maximal surgical resection of disease to less than 2 cm. Its results showed a significant advantage of chemotherapy on 5-year survival (307). Patients who received chemotherapy had a 13% improvement in 2-year progression-free survival (50% vs. 46%) and an 11% improvement in overall 2-year survival (70% vs. 59%) compared with patients treated with whole-abdomen radiation. Although this study was the first to suggest an improvement in outcome for use of adjuvant chemotherapy compared with radiation, toxicity was more prevalent with chemotherapy; patients with gross residual disease were assigned to the radiation arm, almost guaranteeing failure; and overall, 55% of patients experienced a recurrence or progression during the study period (315). GOG184 randomized 552 patients with advanced disease to sixcycles of cisplatin and doxorubicin with or without paclitaxel following surgical debulking and radiotherapy. Side effects were more pronounced with the three-drug regimen, and recurrence-free survival at 36 months was no different between arms (62% vs. 64% for the three-drug regimen). The investigation was closed to patients with stage IV disease during the trial, but subgroup analysis suggested a 50% reduction in recurrence or death in the 57 patients with gross residual disease who received cisplatin, doxorubicin, and paclitaxel (111).
Other GOG studies and the PORTEC-3 trial are investigating the combination of chemotherapy and radiotherapy in advanced or high-risk endometrial cancer. Results of these trials await maturation. GOG258 is comparing chemoradiation followed by chemotherapy versus chemotherapy alone in advanced endometrial cancer. PORTEC-3 is investigating overall survival and failure-free survival of patients with high-risk and advanced stage endometrial carcinoma treated after surgery with chemoradiation followed by chemotherapy versus pelvic radiation alone.
Regarding the use of chemotherapy in high-risk populations with early stage endometrial cancer, the European Organisation for Research and Treatment of Cancer, along with the Nordic Society of Gynecologic Oncology, presented the results of a collaborative trial comparing external radiotherapy versus chemoradiotherapy in patients with stages I or II or IIIC1 (positive pelvic nodes only) and one of the following characteristics: grade 3 or myometrial invasion greater than 50%, DNA aneuploidy, or clearcell or serous histologic type. Performance of a systematic lymphadenectomy was optional. A total of 375 patients were enrolled over a 10-year period and the study was closed early because of slow recruitment. The hazard ratio for progression-free survival was 0.58 (95% CI, 0.34–0.99) in favor of chemoradiation after a median follow-up of 3.5 years (316).