new article out today in OncologySTAT on endometrial cancer

It's so RARE to have new research published on endometrial cancer, that I wanted to share some of the highlights of this new article that came out today. If anyone wants to read the whole article, I saved it since the URL was password protected and I wasn't sure you would be able to access it without OncologySTAT membership. You can email me lindapro@ptd.net if you want me to email you the whole article. I must warn you that, unless you are an 'eyes wide open' kind of girl, several statements in this article may keep you awake at night. But some of it was hopeful and I will post those excerpts here:

(treatment ideas mostly for those with recurrent uterine cancers):

A newer chemotherapeutic agent with activity is ixabepilone, an epothilone B analog. In the GOG 129-P study, ixabepilone resulted in an overall response rate of 12% as second line treatment in advanced endometrial cancer, while stable disease for at least 8 weeks was noted in 30 (60%) patients. Another phase III trial (IXAMPLE2) that is currently recruiting participants randomizes patients to receive second line treatment every 3 weeks with either ixabepilone or standard chemotherapy (paclitaxel or doxorubicin) (ClinicalTrials.gov Identifier: NCT00883116).

The activation of the PI3K/AKT/mTOR signaling pathway induced by the loss of function of PTEN gene, suggests a therapeutic role for the mTOR inhibition. Chemotherapy-naïve patients with advanced, recurrent or metastatic endometrial carcinoma treated with temsirolimus, an mTOR inhibitor, achieved RR of 26% but the result was not correlated with PTEN immunohistochemical expression. Early clinical data of other mTOR inhibitors, including RAD001 (everolimus) and AP2357, have shown promising clinical activity, mainly in the form of disease stabilization [88], [89], [90]. A recent phase II trial of temsirolimus in heavily pretreated patients with advanced endometrial cancer reported a 7% partial response rate and a 44% stable disease rate [91]. Combinations of mTOR inhibitors with hormonal therapy, chemotherapy or other targeted therapies such as epidermal growth factor receptor (EGFR) inhibitors and antiangiogenic agents have been studied and preclinical evidence is encouraging. Early clinical trials are currently underway to evaluate the combination of temsirolimus with topotecan in advanced endometrial cancer. Of note, exposure of endometrial cancer cell lines to an mTOR inhibitor increases progesterone mRNA expression and inhibits ER mRNA expression suggesting a cross-talk between the mTOR pathway and hormone receptor-dependent signal transduction.

Overall, progestins remain a valid option with favorable toxicity profile for patients with well-differentiated (low grade) endometrioid adenocarcinomas with positive progesterone receptors who are not suitable for chemotherapy. In a recent systematic review, 11–56% of grade 1 and 2 tumors were shown to respond to progestins, while RR for PgR positive tumors was usually greater. Toxicity was remarkably low with a rate of grade 3 and 4 events less than 5% [29]. However, it remains unclear why many hormone receptor positive tumors fail to respond to progestins, while a minority of ER/PgR negative tumors actually respond to progestin therapy. Interestingly, a minority of patients treated with progestins can achieve long-term responses exceeding 2 years.

Critical Reviews in Oncology / Hematology
Volume 79, Issue 3 , Pages 278-292, September 2011
Developments in the systemic treatment of endometrial cancer