title: Randomized phase II trial of adjuvant hepatic arterial infusion and systemic chemotherapy with or without bevacizumab in patients with resected hepatic metastases from colorectal cancer.
abstract: OBJECTIVE
  Add systemic bevacizumab (Bev) to adjuvant hepatic arterial infusion (HAI) plus systemic therapy after liver resection to increase recurrence-free survival (RFS).
  
  
  METHODS
  Patients were randomly assigned to HAI plus systemic therapy with or without Bev. If 1-year RFS of ≥ 80% was obtained in Bev arm, then the regimen would be studied further. HAI with fluorodeoxyuridine plus dexamethasone was given on days 1 to 14 of a 5-week cycle. Systemic therapy and Bev 5 mg/kg was delivered on days 15 and 29: oxaliplatin 85 mg/m², leucovorin 400 mg/m², and fluorouracil 2,000 mg/m² infusion for 2 days (if patients received prior oxaliplatin, then irinotecan 150 mg/m² was used). RFS and survival were estimated by using the Kaplan-Meier method and compared by using the log-rank test.
  
  
  RESULTS
  The two arms had similar characteristics: synchronous disease (66% v 63%), more than one metastasis (84% v 74%), and clinical risk score ≥ 3 (50% v 46%) for no Bev versus Bev arms, respectively. With a median follow-up of 30 months, 4-year survival was 85% and 81% (P = .5), and 4-year RFS was 46% versus 37%; 1-year RFS was 83% and 71% (P = .4) for no Bev versus Bev arms. Bilirubin > 3 mg/dL was seen in zero of 38 versus five of 35 patients (P = .02) and biliary stents were placed in zero versus four patients (P = .05) in no Bev versus Bev arms.
  
  
  CONCLUSIONS
  The addition of Bev to adjuvant HAI plus systemic therapy after liver resection did not seem to increase RFS or survival but appeared to increase biliary toxicity. Four-year survival was 85% and 81% for no Bev and Bev arms, respectively.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Weill Medical College, NY, USA. kemenyn@mskcc.org
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kemeny
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Gewirtz
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Dematteo
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006498:Hepatectomy / Q000379:methods; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000556:secondary* / Q000601:surgery; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab