title: 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.
  
  
  OBJECTIVE
  To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma.
  
  
  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.
  
  
  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 reviewers and authors of included studies contacted for further information.
  
  
  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.
  
  
  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.
authors.affiliation: Walsgrave Hospital, Department of Oncology, Clifford Bridge Road, Coventry, UK CV2 2DX. cehumber@doctors.org.uk
authors.forename: C
authors.initials: C
authors.lastname: Humber
authors.forename: J
authors.initials: J
authors.lastname: Tierney
authors.forename: P
authors.initials: P
authors.lastname: Symonds
authors.forename: M
authors.initials: M
authors.lastname: Collingwood
authors.forename: J
authors.initials: J
authors.lastname: Kirwan
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.forename: J
authors.initials: J
authors.lastname: Green
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents