Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma
Abstract
Background
Endometrial adenocarcinoma is a common gynaecological cancer, but a comparatively small proportion of patients present with or develop recurrent or advanced disease. Progestogens are widely used, with little evidence of their efficacy. 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.
Objectives
To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma.
Search methods
The major medical literature databases were searched for all known randomised controlled trials (RCTs), as were trials registers and reference lists of relevant publications.
Selection criteria
RCTs comparing chemotherapy versus another intervention (including different chemotherapy) in advanced disease were considered. Trials of adjuvant treatment or for sarcomatous tumours were excluded.
Data collection and analysis
Data were extracted from the papers by reviewers and authors of included studies contacted for further information.
Main results
Eleven eligible trials were identified which entered 2288 patients between 1974 and 2000. A meta‐analysis of the 6 trials comparing more with less chemotherapy with combination was possible and included 1135 patients. Progression‐free survival (PFS) was significantly improved (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI) 0.71 to 0.90, p = 0.004), but there was only a trend toward improved survival (HR = 0.90, 95% CI 0.80 to 1.03). Toxicity was in general higher with the combination chemotherapy regimens. Only one trial showed a significant survival benefit from the addition of paclitaxel to combination chemotherapy, but this was at the expense of increased toxicity. There was insufficient evidence to assess whether there was any benefit from cytotoxic chemotherapy in terms of symptom control or QOL compared with best supportive care. There were no comparative trials of chemotherapy with endocrine therapy.
Authors' conclusions
The optimum cytotoxic drug regimen for advanced endometrial adenocarcinoma has still to be defined although our review suggests that it may contain paclitaxel or platinum. These mainly North American and European trial populations represent a highly selected subgroup of the 10,000 women dying annually from this disease. Future trials should include measures of QOL and symptom control in addition to PFS and overall survival (OS). They should also consider comparison of endocrine therapy and cytotoxic chemotherapy in patients with no prior drug therapy. Stratification of patients should take into account other prognostic factors including co‐morbidity and prior radiation treatment.
PICOs
Plain language summary
The best drug treatment for women with advanced cancer of the womb is still not clear
These women have a poor prognosis. Giving extra drugs seems to reduce disease progression by a small amount. However, it does not seem to allow women to live longer. Also, more chemotherapy seems to cause a greater amount of serious short‐term side effects. Paclitaxel or platinum drugs may be better than other drugs. The effect of drug therapy on long‐term side effects, control of symptoms and quality of life (QOL) was poorly studied. Also, no studies compared drug therapy with hormone therapy.
