title: Oxaliplatin/fluorouracil-based adjuvant chemotherapy for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and surgery: a systematic review and meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  Previous randomized controlled trials and meta-analyses have demonstrated the ineffectiveness of fluorouracil-based adjuvant chemotherapy for patients with rectal cancer who have undergone neoadjuvant chemoradiotherapy and subsequent surgery. The role of oxaliplatin/fluorouracil-based adjuvant chemotherapy in such patients is unknown. We performed a meta-analysis to evaluate the efficacy of oxaliplatin/fluorouracil-based adjuvant chemotherapy based on a comparison with fluorouracil-based adjuvant chemotherapy for patients with rectal cancer.
  
  
  METHODS
  A literature search of MEDLINE, Embase, Web of Science, Cochrane Library and ClinicalTrials.gov was performed to identify eligible studies. The primary end-point of interest was disease-free survival (DFS). The secondary end-points were overall survival, compliance and the incidence of Grade 3 or 4 toxicity.
  
  
  RESULTS
  The literature search identified four randomized controlled trials that met the inclusion criteria for the meta-analysis, and 2793 patients with pathological TNM or clinical TNM Stage II or III disease were included. The meta-analysis showed that oxaliplatin/fluorouracil-based adjuvant chemotherapy was associated with a significantly improved DFS (hazard ratio 0.85; 95% CI 0.73-0.98; P = 0.03), comparable compliance (OR 1.18; 95% CI 0.95-1.46; P = 0.13) and a higher incidence of vomiting or nausea (OR 2.47; 95% CI 1.21-5.05; P = 0.01). No significant differences were observed between the groups with respect to overall survival and the incidence of leucopaenia, anaemia, thrombocytopaenia and diarrhoea.
  
  
  CONCLUSIONS
  Adjuvant oxaliplatin/fluorouracil-based chemotherapy can improve the DFS of patients after neoadjuvant chemoradiotherapy and radical surgery, compared with adjuvant fluorouracil-based chemotherapy. Data of the longer-term survival outcome are needed.
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: R
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: G
authors.initials: G
authors.lastname: Li
mesh_terms: D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D003967:Diarrhea / Q000139:chemically induced; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D009325:Nausea / Q000139:chemically induced; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012007:Rectum / Q000601:surgery; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil
keywords: Oxaliplatin; adjuvant chemotherapy; advanced rectal cancer; neoadjuvant chemoradiotherapy