title: Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer.
abstract: BACKGROUND
  Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the metastatic organ as compared to systemic chemotherapy (SCT), the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomised controlled trials (RCT) comparing HAI to SCT for the treatment of unresectable liver metastatic disease from colorectal cancer (CRC).
  
  
  OBJECTIVE
  The aim of this work is to quantitatively summarize the results of RCT comparing HAI to SCT for the treatment of unresectable hepatic metastases from CRC.
  
  
  METHODS
  A systematic review of reports published until September 2008 on the findings of RCT that compared HAI to SCT for the treatment of unresectable CRC liver metastases was performed by searching the MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar electronic databases as well as other databanks collecting information on clinical trials.
  
  
  METHODS
  Inclusion criteria were patients with unresectable CRC liver metastases enrolled in RCT comparing HAI to SCT. The outcome measures were tumor response rate and overall survival.
  
  
  METHODS
  Two authors independently carried out study selection and assessment of methodological quality. A third author performed a concordance analysis in order to unravel potential systematic biases.
  
  
  RESULTS
  Ten RCT were identified that met the eligibility criteria. HAI regimens were based on floxuridine (FUDR), 5-fluorouracil or either one of these two fluoropyrimidines in eight and one RCT, respectively. SCT consisted of FUDR or 5-fluorouracil in three and seven RCT, respectively. By pooling the summary data, tumor response rate resulted 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < 0.0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively: the meta-risk of death was not statistically different between the two treatment groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24).
  
  
  CONCLUSIONS
  Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases: in fact, the greater tumor response rate obtained with this HAI regimen does not translate into a survival advantage over fluoropyrimidine alone SCT.
authors: Departement of Oncological & Surgical Sciences, University of Padova, Via Giustiniani 2, Padova, Veneto, Italy, 35128.
authors: Simone
authors: S
authors: Mocellin
authors: Sandro
authors: S
authors: Pasquali
authors: Donato
authors: D
authors: Nitti
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms; D005467:Floxuridine / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007261:Infusions, Intra-Arterial / Q000379:methods*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D016032:Randomized Controlled Trials as Topic
chemical_list: D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D005472:Fluorouracil