Letrozole for endometrial cancer – pro

Medical still life

Endometrial cancer cells often have hormonal receptors and when they do, responsiveness to hormonal blockade may exist.  ER and PR positivity in metastatic endometrial cancer is predictive of response to hormonal therapy, which supports the use of these assays in the management of patients with metastatic disease.  Prospective trials demonstrated overall response rates between 11% and 16% in women treated with medroxyprogesterone acetate or megestrol acetate, with progression-free intervals of only 4 to 6 months. Low histologic grade, receptor positivity, and a prolonged period between initial diagnosis and development of metastatic disease have been shown to predict for response to hormonal treatment. The best studied agents have been progesterone, tamoxifen and thee combination of the two, as well as GHRH antagonists. but a study of GNRH concluded that the evidence is  insufficient to warrant further study of GnRH agonists in the treatment of metastatic endometrial cancer.

The results of two phase II studies of aromatase inhibitors, such as letrozole, carcinoma have been published. The first trial showed a response rate to anastrazole of only 9% in women without prior cytotoxic chemotherapy. A large percentage of the patients enrolled in this trial had high grade histology, which may have contributed to the low response rate. In a Canadian phase II study,  letrozole 2.5 mg daily was given to 32 postmenopausal women with advanced or recurrent metastatic endometrial cancer. Of the 28 patients evaluable for response, 1 (4%) had a complete response, 2 (7%) had a partial response, and 11 (39%) had stable disease for a median duration of 6.7 months (range 3.7 to 19.3 months).

A study: Letrozole in Treating Women With Recurrent or Metastatic Endometrial Cancer, NCT00004251, had been completed but not published.

NCCN does recommend progestational agents:  Megaestrol acetate, tamoxifen and aromatase inhibitors on p. ENDO-B, although it combines this recommendations with the suggestion that when available, clinical trials should be pursued.

Sarah M. Temkin, MD, Gini Fleming, MD Current Treatment of Metastatic Endometrial Cancer Cancer Control. 2009;16(1):38-45.

Humber CE, Tierney JF, Symonds RP, et al. Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration. Ann Oncol. 2007;18(3):409-420.

Wolf K, Slomovitz BM. Novel biologic therapies for the treatment of endometrial cancer. Int J Gynecol Cancer. 2005;15(2):411.

Rose PG, Brunetto VL, Vanle L, et al. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2000;78(2):212-216.

Ma BB, Oza A, Eisenhauer E, et al. The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers: a study of the National Cancer Institute of Canada Clinical Trials Group. Int J Gynecol Cancer. 2004;14(4):650-658.

Jeyarajah AR, Gallagher CJ, Blake PR, et al. Long-term follow-up of gonadotrophin-releasing hormone analog treatment for recurrent endometrial cancer. Gynecol Oncol. 1996;63(1):47-52.

Covens A, Thomas G, Shaw P, et al. A phase II study of leuprolide in advanced/recurrent endometrial cancer. Gynecol Oncol. 1997;64(1):126-129.

2Asbury RF, Brunetto VL, Lee RB, et al. Goserelin acetate as treatment for recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Am J Clin Oncol. 2002;25(6):557-560.

For Lay version see here

For Chemotherapy of on Endometrial cancer see here