Stage III Endometrial Cancer
Standard treatment options:
In general, patients with stage III endometrial cancer are treated with surgery, followed by chemotherapy, or radiation therapy, or both. For many years, radiation therapy was the standard adjuvant treatment for patients with endometrial cancer. However, several randomized trials have confirmed improved survival when adjuvant chemotherapy is used instead of radiation therapy. 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 overall survival (OS) compared with 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%).[Level of evidence: 1iiA]
In a subsequent trial, paclitaxel with doxorubicin had an outcome similar to that of cisplatin with doxorubicin.[2,3] The three-drug regimen (doxorubicin, cisplatin, and paclitaxel) with granulocyte colony-stimulating factor (G-CSF), however, was significantly superior to cisplatin plus doxorubicin: response rates were 57% versus 34%; progression-free survival 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.[2,3][Level of evidence: 1iiDiv]
Given the toxicity and limited efficacy of these regimens, other treatment options have been widely sought. Several observational studies [4,5] and phase II studies [6-9] suggested clinical activity with the combination of platinums and paclitaxel in endometrial cancer patients with measurable disease either following primary surgery or at recurrence. As a result, the Gynecologic Oncology Group (GOG) opened protocol GOG-0209 (NCT000063999), a noninferiority trial that compared the combination of doxorubicin, cisplatin, and paclitaxel (TAP) with G-CSF to carboplatin and paclitaxel. The interim results, currently available in abstract form, showing that carboplatin and paclitaxel is not inferior to TAP have lent credence to the use of carboplatin and paclitaxel as the standard for adjuvant treatment of stage III and IV disease.
Patients with inoperable disease caused by tumor that extends to the pelvic wall may be treated with a combination of chemotherapy and radiation therapy. The usual approach is to use a combination of intracavitary radiation therapy and external-beam radiation therapy.
Patients who are not candidates for either surgery or radiation therapy may be treated with progestational agents. Studies of patterns of failure have found a high rate of distant metastases in the upper abdominal and extra-abdominal sites. For this reason, patients with stage III disease may be candidates for innovative clinical trials.
Treatment options under clinical evaluation:
- The use of biological agents alone, or in combination with chemotherapy, is being investigated in multiple clinical trials.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III 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
- 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. [PUBMED Abstract]
- 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. [PUBMED Abstract]
- 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. [PUBMED Abstract]
- Arimoto T, Nakagawa S, Yasugi T, et al.: Treatment with paclitaxel plus carboplatin, alone or with irradiation, of advanced or recurrent endometrial carcinoma. Gynecol Oncol 104 (1): 32-5, 2007. [PUBMED Abstract]
- Sovak MA, Hensley ML, Dupont J, et al.: Paclitaxel and carboplatin in the adjuvant treatment of patients with high-risk stage III and IV endometrial cancer: a retrospective study. Gynecol Oncol 103 (2): 451-7, 2006. [PUBMED Abstract]
- Hoskins PJ, Swenerton KD, Pike JA, et al.: Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol 19 (20): 4048-53, 2001. [PUBMED Abstract]
- Pectasides D, Xiros N, Papaxoinis G, et al.: Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. Gynecol Oncol 109 (2): 250-4, 2008. [PUBMED Abstract]
- Nomura H, Aoki D, Takahashi F, et al.: Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041). Ann Oncol 22 (3): 636-42, 2011. [PUBMED Abstract]
- Dimopoulos MA, Papadimitriou CA, Georgoulias V, et al.: Paclitaxel and cisplatin in advanced or recurrent carcinoma of the endometrium: long-term results of a phase II multicenter study. Gynecol Oncol 78 (1): 52-7, 2000. [PUBMED Abstract]
- Greven KM, Curran WJ Jr, Whittington R, et al.: Analysis of failure patterns in stage III endometrial carcinoma and therapeutic implications. Int J Radiat Oncol Biol Phys 17 (1): 35-9, 1989. [PUBMED Abstract]