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Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review.

ABSTRACT: Introduction: Hormonal therapy in endometrial cancer (EC) is used for patients who wish to preserve fertility and for patients with advanced or recurrent disease in a palliative setting. First line hormonal therapy consists of treatment with progestins, which has a response rate of 25% in an unselected population. Treatment with anti-estrogens is an alternative hormonal therapy option, but there is limited data on the effect and side-effects of anti-estrogens in EC. Therefore, we performed a systematic review to investigate the response rate and toxicity of anti-estrogenic therapy in patients with endometrial cancer. Methods: A systematic search in electronic databases was performed to identify studies on selective estrogen receptor modulators (SERM) and down-regulators (SERD) and aromatase inhibitors that reported on response rates (RR) among EC patients. Outcome in estrogen receptor (ER) positive and negative disease was assessed independently. Results: Sixteen studies on advanced stage and recurrent EC were included. Ten studies investigated anti-estrogen monotherapy and seven investigated a combination of anti-estrogenic drugs with either progestin or targeted treatment. Due to heterogeneity in patient population, no meta-analysis was performed. The median age of the patients in the included studies ranged from 61 to 71 years and the proportion of low grade tumors ranged from 38 to 80%. The RR for tamoxifen ranged from 10 to 53%, for other SERMs and SERDs 9-31%, for aromatase inhibitors from 8 to 9%, for combined tamoxifen/progestin treatment 19-58%, for combined chemo- and hormonal therapy 43% and for combination of anti-estrogenic treatment with mammalian target of rapamycin (mTOR) inhibitors 14-31%. Toxicity consisted mainly of nausea and thrombotic events and was higher in combination therapy of chemotherapy and hormonal therapy and hormonal therapy and mTOR inhibitors compared to other therapies. Conclusion: Tamoxifen or a combination of tamoxifen and progestin should be the preferred choice when selecting second line hormonal treatment because the RRs are similar to first line progestin treatment and the toxicity is low. The response can be optimized by selecting patients with endometrioid tumors and positive estrogen receptor status, which should be based on a pretreatment biopsy.

SUBMITTER: van Weelden WJ

PROVIDER: S-EPMC6513972 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cancer cachexia (CC) is a multifactorial syndrome driven by inflammation, defined by ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support. CC leads to progressive functional impairment, with its clinical management complicated and limited therapeutic options available. The objective of this review was to assess the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) on patient-centred outcomes in patients with CC. In 2013, two systematic reviews concluded that there was insufficient evidence to recommend NSAIDs for clinical management of CC outside of clinical trials. However, clinical trials of multi-component CC interventions have included NSAIDs as an intervention component, so an up-to-date assessment of the evidence for NSAIDs in the treatment of CC is warranted. Four databases (MEDLINE, EMBASE, CENTRAL and CINAHL) and three trial registers (clinicaltrials.gov, WHO ICTRP and ISRCTN) were searched on 16 December 2022. Randomized controlled trials (RCTs) comparing any NSAID (any dose or duration) with a control arm, in adult patients with CC, reporting measures of body weight, body composition, nutrition impact symptoms, inflammation, physical function or fatigue, were eligible for inclusion. Primary outcomes (determined with patient involvement) were survival, changes in muscle strength, body composition, body weight and quality of life. Included studies were assessed for risk of bias using the Revised Cochrane risk-of-bias tool for randomized trials. Five studies were included, which investigated Indomethacin (n = 1), Ibuprofen (n = 1) and Celecoxib (n = 3). Four studies were judged to be at high risk of bias for all outcomes, with one study raising concerns for most outcomes. Considerable clinical and methodological heterogeneity amongst the studies meant that meta-analysis was not appropriate. There was insufficient evidence to determine whether Indomethacin or Ibuprofen is effective or safe for use in patients with CC; RCTs with lower risk of bias are needed. Celecoxib studies indicated it was safe for use in this population at the doses tested (200-400 mg/day) but found contrasting results regarding efficacy, potentially reflecting heterogeneity amongst the studies. There is inadequate evidence to recommend any NSAID for CC. While current clinical trials for CC treatments are shifting towards multi-component interventions, further research to determine the efficacy and safety of NSAIDs alone is necessary if they are to be included in such multi-component interventions. Furthermore, the lack of data on patient-determined primary outcomes in this review highlights the need for patient involvement in clinical trials for CC.

Project description:ObjectiveWhile primary cytoreductive surgery (PCS) is considered the standard of care for women who present with stage IV endometrial cancer, neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) has emerged as an alternative treatment strategy. We summarized the literature and compared outcomes of PCS compared to NACT and ICS.MethodsWe conducted a systematic search on PubMed, Embase, Web of Science, and Scopus for articles published from January 1, 1990 to December 31, 2020. Key search terms included multiple descriptors of advanced disease status in combination with "endometrial cancer" and "neoadjuvant chemotherapy". Our review included studies that examined survival and surgical outcomes of patients with stage III or IV endometrial cancer treated with neoadjuvant chemotherapy followed by interval cytoreductive surgery versus those who received primary cytoreductive surgery. We excluded studies examining only patients with leiomyosarcomas, carcinosarcomas, and stromal sarcomas due to the biologic heterogeneity of these malignancies.ResultsThe nine included studies encompassed 5,844 patients, of which 1,317 (22.5%) received NACT and 4,527 received PCS (77.5%). With the exception of a single study, all were retrospective observational studies or case series. Use of NACT in patients with stage IV EC increased from 16.0% in 2010 to 23.9% in 2015. Five studies analyzed median overall survival and all but one reported no significant difference between NACT + ICS vs. PCS. Optimal cytoreduction (<1 cm of residual disease) rates were similar across both treatment groups in three separate analyses, however pooled data suggest improved rates of optimal cytoreduction for NACT + ICS vs. PCS patients (81.9% vs. 51.5% respectively). Patients receiving NACT experienced significantly shorter hospital admissions and lower operative times compared to PCS counterparts.ConclusionsNACT followed by ICS reduces perioperative morbidity while offering similar overall survival.

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Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review.

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