Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma.
BACKGROUND
Although endometrial adenocarcinoma is a common gynaecological cancer, a comparatively small proportion of patients present with, or develop, recurrent or advanced disease. However, for those women whose disease does progress or recur the prognosis is poor and the best treatment is yet to be identified. Co-morbidity, including obesity and cardiac disease, and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents.


OBJECTIVE
To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma.


METHODS
Systematic searches of MEDLINE, EMBASE, CENTRAL and the Cochrane Gynaecological Cancer specialist trials register were conducted to identify all eligible randomised controlled trials (RCTs).Databases were searched from 1966 to January 2012. Literature searches were supplemented with searches of relevant trials registers and conference proceedings.


METHODS
RCTs comparing chemotherapy versus another intervention (including different chemotherapy) in advanced disease were considered. Trials of adjuvant treatment or for sarcomatous tumours were excluded.


METHODS
Data were extracted from the papers by review authors and authors of included studies contacted for further information.


RESULTS
Fourteen eligible trials, which recruited patients between 1974 and 2005, were identified, eight of which compared 'more' with 'less' chemotherapy. Results from these eight trials, including 1519 patients, showed that treatment consisting of 'more' chemotherapy was associated with longer overall survival (OS) (hazard ratio (HR) 0.86; 95% confidence intervals (CI) 0.77 to 0.96; P = 0.005) and with longer progression-free survival (PFS) (n = 1526; HR 0.82; 95% CI 0.74 to 0.90; P < 0.0001). However, serious acute toxicities were more common in women randomised to the more-intense chemotherapy regimens.There was no evidence to suggest that any particular doublet chemotherapy was better (or worse) than any other, or that any single-agent chemotherapy was better (or worse) than another; however, data for these two comparisons were limited. There were no comparative trials of chemotherapy with endocrine therapy or best supportive care alone.


CONCLUSIONS
This review suggests that more-intense chemotherapy regimens may improve both OS and PFS for women with advanced or recurrent endometrial cancer. However, owing to inconsistencies between cytotoxic drug combinations that have been assessed in randomised trials to date, the optimum regimen has still to be defined. Future trials should aim to include measures of quality of life (QoL) and symptom control in addition to survival and progression outcomes.
Meta-analysis Group, MRC Clinical Trials Unit, London, UK. cv@ctu.mrc.ac.uk. Hidden.
Claire L
CL
Vale
Jayne
J
Tierney
Sarah J
SJ
Bull
Paul R
PR
Symonds
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents