title: Adjuvant radiotherapy and/or chemotherapy after surgery for uterine carcinosarcoma.
abstract: BACKGROUND
  Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of women with advanced uterine carcinosarcoma is poor with a pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence.
  
  
  OBJECTIVE
  To evaluate the effectiveness and safety of adjuvant radiotherapy and/or systemic chemotherapy in the management of uterine carcinosarcoma.
  
  
  METHODS
  We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), 2012, Issue 10, MEDLINE and EMBASE up to November 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.
  
  
  METHODS
  Randomised controlled trials (RCTs) comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma.
  
  
  METHODS
  Two review authors independently abstracted data and assessed risk of bias. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy were pooled in random-effects meta-analyses.
  
  
  RESULTS
  Three trials met the inclusion criteria and these randomised 579 women, of whom all were assessed at the end of the trials. Two trials assessing 373 participants with stage III to IV persistent or recurrent disease, found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide, after adjustment for performance status (HR = 0.75, 95% confidence interval (CI): 0.60 to 0.94 and HR = 0.72, 95% CI: 0.58 to 0.90 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, where significantly more women experienced these ailments in the combination therapy group than the Ifosamide group (RR = 3.53, 95% CI: 1.33 to 9.37).In one trial there was no statistically significant difference in the risk of death and disease progression in women who received whole body irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95% CI: 0.48 to 1.05 and HR = 0.79, 95% CI: 0.53 to 1.18 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of haematological and neuropathy morbidities, where significantly less women experienced these morbidities in the whole body irradiation group than the chemotherapy group (RR= 0.02, 95% CI: 0.00 to 0.16) for haematological morbidity and all nine women in the trial experiencing neuropathy morbidity were in the chemotherapy group).
  
  
  CONCLUSIONS
  In advanced stage metastatic uterine carcinosarcoma as well as recurrent disease adjuvant combination, chemotherapy with ifosfamide should be considered. Combination chemotherapy with ifosfamide and paclitaxel is associated with lower risk of death compared with ifosfamide alone. In addition, radiotherapy to the abdomen is not associated with improved survival.
authors: Gynaecological Oncology, Princess Alexandra Wing, Royal Cornwall Hospital, Truro, UK. Khadra.Galaal@rcht.cornwall.nhs.uk.
authors: Khadra
authors: K
authors: Galaal
authors: Esther
authors: E
authors: van der Heijden
authors: Keith
authors: K
authors: Godfrey
authors: Raj
authors: R
authors: Naik
authors: Ali
authors: A
authors: Kucukmetin
authors: Andrew
authors: A
authors: Bryant
authors: Nagindra
authors: N
authors: Das
authors: Alberto D
authors: AD
authors: Lopes
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D002296:Carcinosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D017239:Paclitaxel / Q000627:therapeutic use; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D018906:Antineoplastic Agents, Alkylating; D017239:Paclitaxel; D007069:Ifosfamide