title: The impact of complete chemotherapy stop on the overall survival of patients with advanced colorectal cancer in first-line setting: A meta-analysis of randomized trials.
abstract: BACKGROUND
  The impact of the duration of chemotherapy on the overall survival of patients with metastatic colorectal cancer (mCRC) is controversial and studies have failed to define a clear standard.
  
  
  METHODS
  We searched medical literature databases and oncology conferences proceedings for randomized controlled trials (RCT) that compared the overall survival of mCRC patients who received continuous first-line chemotherapy until disease progression versus those who were offered complete treatment stop after a fixed number of cycles. Studies including targeted agents were also included. A meta-analysis of reported hazard ratios (HRs) for survival was performed.
  
  
  RESULTS
  We retrieved 240 trials, of which six were eligible and five were included in the pooled analysis of overall survival (N = 3061). The overall survival between continuously delivered chemotherapy and complete stop was not statistically different (HR = 0.93, 95% CI 0.85-1.02; p = 0.12; I² = 5%). The results are similar when we analyzed separately the trials performing randomization before versus after induction therapy. The median chemotherapy free interval in the complete stop group was 3.9 months (3.6-4.3 months). Chemotherapy administered until progression was associated with more adverse effects and impaired quality of life.
  
  
  CONCLUSIONS
  Compared with first-line continuous chemotherapy administered until disease progression, complete treatment stop did not have a detrimental impact on the overall survival of patients with mCRC. Identification of predictive biomarkers could help clinicians to select the patients who would benefit from continuous cancer-directed therapies.
authors.affiliation: a Department of Radiology and Oncology , Instituto do Cancer do Estado de Sao Paulo , Sao Paulo , Brazil.
authors.forename: Allan Andresson Lima
authors.initials: AA
authors.lastname: Pereira
authors.affiliation: a Department of Radiology and Oncology , Instituto do Cancer do Estado de Sao Paulo , Sao Paulo , Brazil.
authors.forename: Juliana Florinda de Mendonça
authors.initials: JF
authors.lastname: Rego
authors.affiliation: a Department of Radiology and Oncology , Instituto do Cancer do Estado de Sao Paulo , Sao Paulo , Brazil.
authors.forename: Rodrigo Ramela
authors.initials: RR
authors.lastname: Munhoz
authors.affiliation: a Department of Radiology and Oncology , Instituto do Cancer do Estado de Sao Paulo , Sao Paulo , Brazil.
authors.forename: Paulo Marcelo
authors.initials: PM
authors.lastname: Hoff
authors.affiliation: b Universidade Estadual de Campinas , Campinas , Brazil.
authors.forename: Andre Deeke
authors.initials: AD
authors.lastname: Sasse
authors.affiliation: a Department of Radiology and Oncology , Instituto do Cancer do Estado de Sao Paulo , Sao Paulo , Brazil.
authors.forename: Rachel P
authors.initials: RP
authors.lastname: Riechelmann
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D004334:Drug Administration Schedule; D006801:Humans; D009362:Neoplasm Metastasis; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D028761:Withholding Treatment