title: Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer.
abstract: BACKGROUND
  Current standard treatment for patients with cervical cancer who have locally advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IVA) is concurrent chemoradiation therapy (CCRT). However, less than two-thirds of patients in this group survive for longer than five years post treatment. Adjuvant chemotherapy (ACT) can be given in an attempt to improve survival by eradicating residual disease in the pelvis and treating occult disease outside the pelvic radiation field. However, inconsistency in trial design, inclusion criteria for participants, interventions and survival benefit has been noted among trials of ACT after CCRT for locally advanced cervical cancer (LACC).
  
  
  OBJECTIVE
  To evaluate the effect of adjuvant chemotherapy (ACT) after concurrent chemoradiation (CCRT) on survival of women with locally advanced cervical cancer compared with CCRT alone.
  
  
  METHODS
  We searched the Cochrane Gynaecological Review Group Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and conference proceedings to March 2014. We handsearched citation lists of relevant studies.
  
  
  METHODS
  Randomised controlled trials (RCTs) comparing CCRT alone versus CCRT plus ACT were included. Patients were diagnosed with cervical cancer FIGO stage IIB to IVA with a histopathology of squamous cell carcinoma, adenosquamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma.
  
  
  METHODS
  Two review authors (ST, KK) selected relevant trials, extracted data, assessed risk of bias independently, compared results and resolved disagreements by discussion.
  
  
  RESULTS
  We identified two RCTs involving 978 women with cervical cancer stage IIB to IVA. As the trials were significantly different clinically, we did not perform meta-analyses. One industry-funded trial involving 515 women compared CCRT (cisplatin) versus CCRT (cisplatin and gemcitabine) plus ACT (two additional cycles). This trial reported significant improvement in progression-free survival (PFS) and overall survival (OS) in women who were given CCRT plus ACT compared with those treated with CCRT alone: Three-year PFS was 74.4% versus 65.0% (hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.49 to 0.95, P value 0.027), and three-year OS was 80% versus 69% (HR 0.68, 95% CI 0.49 to 0.95, P value 0.022). However, as the CCRT chemotherapy differed between the two arms, we considered the findings to be at high risk of bias.The second trial was a four-arm study from which we extracted data on 463 women in two study arms receiving CCRT (intravenous mitomycin C and oral 5-fluorouracil (5-FU)) or CCRT plus ACT (oral 5-FU for three cycles). The HR for OS in women who received ACT after CCRT compared with the HR for OS in those who were given CCRT alone was 1.309 (95% CI 0.795 to 2.157), and the HR for disease-free survival (DFS) was 1.125 (95% CI 0.799 to 1.586).Haematological adverse events were more common in the ACT arms of both trials. Quality of life (QoL) was not reported in either trial.
  
  
  CONCLUSIONS
  With limited data from only two trials, we found insufficient evidence to support the use of ACT after CCRT. Future large trials are required to demonstrate efficacy, toxicities and QoL.
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj  University, 681 Samsen Road, Dusit District, Bangkok, 10300, Thailand. siriwanonco@yahoo.com.
authors.forename: Siriwan
authors.initials: S
authors.lastname: Tangjitgamol
authors.forename: Kanyarat
authors.initials: K
authors.lastname: Katanyoo
authors.forename: Malinee
authors.initials: M
authors.lastname: Laopaiboon
authors.forename: Pisake
authors.initials: P
authors.lastname: Lumbiganon
authors.forename: Sumonmal
authors.initials: S
authors.lastname: Manusirivithaya
authors.forename: Busaba
authors.initials: B
authors.lastname: Supawattanabodee
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000379:methods* / Q000401:mortality; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D016032:Randomized Controlled Trials as Topic; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016685:Mitomycin; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine