Adjuvant progestagen therapy improves survival in patients with endometrial cancer after hysterectomy. Results of one-institutional prospective clinical trial. A randomized trial of adjuvant progestagen in early endometrial cancer. Adjuvant progestogen therapy in the primary definitive treatment of endometrial cancer. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies. Efficacy of sequential cyclical hormonal therapy in endometrial cancer and its correlation with steroid hormone receptor status. A randomized trial of progestogens in the primary treatment of endometrial carcinoma. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial. Prospective randomized study of aminoglutethimide (AG) versus medroxyprogesterone acetate (MPA) versus AG+MPA in generalized breast cancer. Multidrug treatment of advanced and recurrent endometrial carcinoma: a Gynecologic Oncology Group study.
A prospective study was conducted to determine the effectiveness of adjuvant hormonotherapy in endometrial cancer after surgery. Two hundred and five patients were randomly assigned to adjuvant progestagen treatment or were given no additional therapy. The follow-up was 5-years. We concluded that there was evidence of gain from adjuvant progestagen therapy in postoperative endometrial cancer. The group of patients who received progestagens had significantly longer survival than the control group without hormonotherapy (Logrank test; P < 0.001). A randomized, controlled trial was designed to determine whether adjuvant progestagen therapy improves survival in patients with Stage I or Stage II endometrial cancer. After surgery, 1148 patients were randomly assigned to adjuvant treatment with progesterone or were given no additional therapy. The duration of follow-up ranged from 42 to 132 months (median follow-up, 72 months). Crude survival and relapse rates were similar for both groups. Death due to intercurrent disease was higher in the progesterone group (P = 0.04). The median survival of the group of patients with cancer-related death was higher in the progestagen group than in the control group (30 and 22 months, respectively; P = 0.03). In 461 high-risk patients, a tendency towards fewer cancer-related deaths and a better disease-free survival in the treatment group was observed, but crude survival was unchanged. We conclude that there is little to gain from adjuvant progestagen therapy in patients with low-risk endometrial cancer, and that further studies are needed in high-risk patients. nan Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled.
                Patients (n=540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy.
                In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41-0.99; P=0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P=0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P=0.01).
                Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.
                Copyright 2010 Elsevier Ltd. All rights reserved. Forty-six eligible women with metastatic endometrial cancer were randomly allocated to receive monthly cycles of either CAF (cyclophosphamide, adriamycin, 5-fluorouracil) or CAF plus Provera 200 mg daily for 3 weeks followed cyclically by Tamoxifen 20 mg daily for 3 weeks. Overall response rates of 15 and 43% were seen with CAF and CAF plus hormonal therapy. Using a multivariate analysis of the results, this difference is significant (P value 0.05). In 8 patients with operable endometrial cancer, negative estrogen receptor concentration (ER less than 15 fmole/mg protein) and Grade 3 disease, the clinical course was aggressive in 4 patients with systemic and local relapse. In 10 other similar patients (negative ER and Grade 3) who received adjuvant cyclical hormonal therapy only 1 relapsed and the other 9 are disease-free for an average of more than 31 months. Sequential cyclical hormonal therapy with ER and progesterone receptor analysis has a place in the management of endometrial carcinoma. A randomized trial was arranged in Yorkshire to assess whether progestogens would improve survival as part of the primary treatment of endometrial carcinoma, in conjunction with surgery and radiotherapy. A total of 429 patients was randomized on diagnosis to the progestogen or control group and treated locally according to an agreed protocol. All the patients are now more than 1 year after operation and over half are more than 5 years after operation. The projected overall 5-year survival rate is 76% but contrary to expectation there is no statistically significant difference in survival between the patients treated with progestogens and the control group even after statistical adjustment for known prognostic factors. Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m(-2)), doxorubicin (45 mg m(-2)), cyclophosphamide (600 mg m(-2)) every 28 days for five cycles, or external RT (45-50 Gy on a 5 days week(-1) schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66-1.36; P = 0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63-1.23; P = 0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited. Eighty-five postmenopausal women with metastatic breast cancer were randomized to receive aminoglutethimide (AG), medroxyprogesterone acetate (MPA), or AG+MPA. Patients with aggressive visceral disease were excluded. Response was observed in 36% of the patients in the AG treatment group, 31% in the MPA treatment group, and 47% in the combination treatment group. Statistical analysis showed that the percentage of responders was not different among the three treatment groups. Similarly, the duration of response did not differ. Toxicity of all three regimens was moderate, not necessitating discontinuation of treatment. In conclusion, AG, MPA and the combination of AG+MPA were found to be equally effective therapies for metastatic breast cancer in postmenopausal women with nonaggressive visceral disease. The lack of statistically significant superiority of the combination of AG+MPA suggests that sequential endocrine monotherapies may be more beneficial than combined hormonotherapies for this patient population. Patients (358) with advanced (FIGO stages III and IV) or recurrent endometrial cancer were treated with one of two regimens: 1) melphalan and 5-fluorouracil daily for four days, repeated every four weeks with megace daily for eight weeks and 2) adriamycin, 5-fluorouracil, and cyclophosphamide, intravenous bolus every 21 days with megace daily for eight weeks. All patients were randomized except for 63 with known cardiac disease who were assigned to regimen 1 (to avoid adriamycin) and studied separately. Stratification was effected for performance status, history of previous progestational therapy, presence or absence of measurable disease, and stage of disease. The objective response rate in those with measurable disease was 36.8% in both groups; 36.8% of each group had stable disease, and only 26.4% progressed on treatment. Response was unaffected by site of recurrence, time to first recurrence, presence or absence of previous treatment by progestational or radiation therapy, or age. Grade of tumor and performance status did affect response, although 44 of 57 objective responders had undifferentiated tumors. The two combinations achieved response rapidly, required careful supervision, and were especially useful in treating patients with usually poor prognostic features.
There is no evidence to support the use of adjuvant progestagen therapy in the primary treatment of endometrial cancer.