Recurrent Endometrial Cancer
For patients with localized recurrences (pelvis and periaortic lymph nodes) or distant metastases in selected sites, radiation therapy may be an effective palliative therapy. In rare instances, pelvic radiation therapy may be curative in pure vaginal recurrence when no prior radiation therapy has been used. Patients positive for estrogen and progesterone receptors respond best to progestin therapy. Among 115 patients with advanced endometrial cancer who were treated with progestins, 75% (42 of 56 patients) of those with detectable progesterone receptors in their tumors before treatment responded, compared with only 7% without detectable progesterone receptors (4 of 59 patients). A receptor-poor status may predict not only poor response to progestins but also a better response to cytotoxic chemotherapy. Evidence suggests that tamoxifen (20 mg twice a day) will give a response rate of 20% in those who do not respond to standard progesterone therapy.
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). 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 with whole-abdominal radiation therapy (adjusted hazard ratio, 0.68; 95% confidence interval limits, 0.52–0.89; P = .02; 5-year survival rate of 55% vs. 42%).[Level of evidence: 1iiA] In a subsequent trial, paclitaxel with doxorubicin had a similar outcome to cisplatin with doxorubicin.[6,7] 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.[6,7][Level of evidence: 1iiDiv]
Biologic agents under evaluation for patients with advanced and recurrent endometrial cancer include:
Clinical trials are appropriate for patients whose disease recurs with distant metastases and who are unresponsive to hormonal therapy. Doxorubicin is the most active anticancer agent employed, with useful but temporary responses obtained in as many as 33% of patients with metastatic disease. Paclitaxel, in combination with platinums or as a single agent, also has significant activity.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent 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.
- Kauppila A: Oestrogen and progestin receptors as prognostic indicators in endometrial cancer. A review of the literature. Acta Oncol 28 (4): 561-6, 1989. [PUBMED Abstract]
- Kauppila A, Friberg LG: Hormonal and cytotoxic chemotherapy for endometrial carcinoma. Steroid receptors in the selection of appropriate therapy. Acta Obstet Gynecol Scand Suppl 101: 59-64, 1981. [PUBMED Abstract]
- Quinn MA, Campbell JJ: Tamoxifen therapy in advanced/recurrent endometrial carcinoma. Gynecol Oncol 32 (1): 1-3, 1989. [PUBMED Abstract]
- 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. [PUBMED Abstract]
- 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]
- Aghajanian C, Sill MW, Darcy KM, et al.: Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol 29 (16): 2259-65, 2011. [PUBMED Abstract]
- Alvarez EA, Brady WE, Walker JL, et al.: Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 129 (1): 22-7, 2013. [PUBMED Abstract]
- Cornelison TL, Baker TR, Piver MS, et al.: Cisplatin, adriamycin, etoposide, megestrol acetate versus melphalan, 5-fluorouracil, medroxyprogesterone acetate in the treatment of endometrial carcinoma. Gynecol Oncol 59 (2): 243-8, 1995. [PUBMED Abstract]
- 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. [PUBMED Abstract]