title: Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481).
abstract: OBJECTIVE
  Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome.
  
  
  METHODS
  In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers.
  
  
  RESULTS
  Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade > or = 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or > or = 4, the median survival was 24 and 14 months, respectively (P = .17).
  
  
  CONCLUSIONS
  HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. kemenyn@mskcc.org
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kemeny
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: Donna R
authors.initials: DR
authors.lastname: Hollis
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: Robert S
authors.initials: RS
authors.lastname: Warren
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Naughton
authors.forename: Jane C
authors.initials: JC
authors.lastname: Weeks
authors.forename: Elin R
authors.initials: ER
authors.lastname: Sigurdson
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Zhang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mayer
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D002955:Leucovorin; D005472:Fluorouracil