Stage IV Endometrial Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Standard treatment options:

Treatment of patients with stage IV endometrial cancer is dictated by the site of metastatic disease and symptoms related to disease sites. For bulky pelvic disease, radiation therapy consisting of a combination of intracavitary and external-beam radiation therapy is used. When distant metastases, especially pulmonary metastases, are present, hormonal therapy is indicated and useful.

The most common hormonal treatment has been progestational agents, which produce good antitumor responses in as many as 15% to 30% of patients. These responses are associated with significant improvement in survival. Progesterone and estrogen hormone receptors have been identified in endometrial carcinoma tissues. Responses to hormones are correlated with the presence and level of hormone receptors and the degree of tumor differentiation. Standard progestational agents include hydroxyprogesterone, medroxyprogesterone, and megestrol.[1]

Several randomized trials by the Gynecologic Oncology Group have utilized the known antitumor activity of doxorubicin. The addition of cisplatin to doxorubicin increased response rates and progression-free survival (PFS) over doxorubicin alone but without an effect on overall survival (OS).[2] However, in a trial conducted in a subset of patients with stage III or IV disease with residual tumors smaller than 2 cm and no parenchymal organ involvement, the use of the combination of cisplatin and doxorubicin resulted in improved OS compared to whole-abdominal radiation therapy (adjusted hazard ratio = 0.68; 95% confidence interval limits, 0.52–0.89; P = .02; 5-year survival rates of 55% vs. 42%).[3][Level of evidence: 1iiA] In a subsequent trial, paclitaxel with doxorubicin had a similar outcome to cisplatin with doxorubicin.[4,5] The three-drug regimen (doxorubicin, cisplatin, and paclitaxel) with granulocyte colony-stimulating factor, however, was significantly superior to cisplatin plus doxorubicin: response rates were 57% versus 34%, PFS was 8.3 months versus 5.3 months, and OS was 15.3 months versus 12.3 months, respectively. The superior regimen was associated with a 12% grade 3 and a 27% grade 2 peripheral neuropathy.[4,5][Level of evidence: 1iiDiv]

Treatment options under clinical evaluation:

No standard chemotherapy program is available for patients with metastatic uterine cancer, though doxorubicin has activity. Some studies have demonstrated activity of doxorubicin-containing combinations, though no prospective comparison of single-agent versus combination chemotherapy is available that has demonstrated superiority of the combinations.[6,7]

Paclitaxel has demonstrated antitumor activity and has been evaluated.[8]

All patients with advanced disease should be considered for clinical trials that evaluate single-agent or combination therapy for this disease.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV endometrial carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Lentz SS: Advanced and recurrent endometrial carcinoma: hormonal therapy. Semin Oncol 21 (1): 100-6, 1994.
2. Thigpen JT, Brady MF, Homesley HD, et al.: Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 22 (19): 3902-8, 2004.
3. Randall ME, Filiaci VL, Muss H, et al.: Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 24 (1): 36-44, 2006.
4. Fleming GF, Brunetto VL, Cella D, et al.: Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 22 (11): 2159-66, 2004.
5. Fleming GF, Filiaci VL, Bentley RC, et al.: Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol 15 (8): 1173-8, 2004.
6. Hancock KC, Freedman RS, Edwards CL, et al.: Use of cisplatin, doxorubicin, and cyclophosphamide to treat advanced and recurrent adenocarcinoma of the endometrium. Cancer Treat Rep 70 (6): 789-91, 1986.
7. Seski JC, Edwards CL, Herson J, et al.: Cisplatin chemotherapy for disseminated endometrial cancer. Obstet Gynecol 59 (2): 225-8, 1982.
8. Ball HG, Blessing JA, Lentz SS, et al.: A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 62 (2): 278-81, 1996.