What are the chemotherapeutic options for women with advanced or recurrent endometrial cancers?

The group unanimously endorsed the ESMO guidelines 20134on the treatment of advanced endometrial cancer as it was felt to be the most comprehensive among the 3 chosen guidelines.

Paclitaxel and platinum-based combination chemotherapy (carboplatin/paclitaxel) is the preferred first line chemotherapy regimen for patients with advanced or recurrent endometrial cancer. In non-randomized trials, paclitaxel with carboplatin/cisplatin demonstrated a response rate of more than 60% and prolonged survival compared with historical non-paclitaxel based combination therapy. The results of GOG 2093showed that the carboplatin and paclitaxel combination is non-inferior to the triple drug regimen in response rate and PFS, and is also less toxic.

The use of hormonal therapy can also be considered in certain circumstances. Hormonal therapy, mainly progestins, and less commonly tamoxifen or aromatase inhibitors, are recommended for endometrioid type histology only. The predictors of response include well-differentiated tumours, a long disease free interval and site of disease (pulmonary metastases). The overall response rate to progestin is about 25%.

Endometrial cancer recurring after first line chemotherapy is usually chemo-resistant. Various agents have been tested in small phase II trials. The PI3K/Akt/mTOR pathway is frequently upregulated in endometrial cancer because of the loss of the tumour suppression gene PTEN. There is emerging phase II data to support the role of mTOR inhibitors in patients with metastatic or recurrent endometrioid endometrial cancer following failure of first line chemotherapy.5The mTOR inhibitor temsirolimus has been reported to have a 24% response rate in chemotherapy naive patients. In previously treated patients, the response rate to temsirolimus is 4% with 46% disease stabilization.5Predictive factors of response to mTOR inhibitors have not yet been identified.

Our recommendation is to first treat with hormonal therapy for patients with endometrioid type histology who are asymptomatic with low volume disease. Symptomatic disease or high grade/large volume disease should be treated with platinum and taxane combination chemotherapy.