title: Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes.
abstract: OBJECTIVE
  Evaluate conversion rate of patients with unresectable colorectal-liver metastasis to complete resection with hepatic-arterial infusion plus systemic chemotherapy including bevacizumab (Bev).
  
  
  METHODS
  Forty-nine patients with unresectable colorectal liver metastases (CRLM) were included in a single-institution phase II trial. Conversion to resection was the primary outcome. Secondary outcomes included overall survival (OS), progression-free survival, and response rates. Multivariate and landmark analyses were performed to evaluate survival differences between resected and nonresected patients.
  
  
  RESULTS
  Median number of tumors was 14 and 65% were previously treated patients. A high biliary toxicity rate was found in the first 24 patients whose treatment included Bev. The remaining 25 patients were treated without Bev. Overall response rates were 76% (4 complete responses). Twenty-three patients (47%) achieved conversion to resection at a median of 6 months from treatment initiation. Median OS and progression-free survival for all patients were 38 (95% confidence interval: 28 to not reached) and 13 months (95% confidence interval: 7-16). Bev administration did not impact outcome. Conversion was the only factor associated with prolonged OS and progression-free survival in multivariate analysis. On landmark analysis, patients who had undergone resection had longer OS than those who did not undergo resection (3-year OS: 80% vs 26%). Currently, 10 of 49 (20%) patients have no evidence of disease (NED) at a median follow-up of 39 months (32-65 months).
  
  
  CONCLUSIONS
  In patients with extensive unresectable CRLM, the majority of whom were previously treated, 47% were able to undergo complete resection after combined HAI and systemic therapy. Conversion to resection is associated with prolonged survival.
authors.affiliation: Departments of *Surgery †Medicine; and ‡Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Michael I
authors.initials: MI
authors.lastname: DʼAngelica
authors.forename: Camilo
authors.initials: C
authors.lastname: Correa-Gallego
authors.forename: Philip B
authors.initials: PB
authors.lastname: Paty
authors.forename: Andrea
authors.initials: A
authors.lastname: Cercek
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Gewirtz
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Chou
authors.forename: Marinella
authors.initials: M
authors.lastname: Capanu
authors.forename: T Peter
authors.initials: TP
authors.lastname: Kingham
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.forename: Nancy
authors.initials: N
authors.lastname: Kemeny
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006498:Hepatectomy; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D005467:Floxuridine; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin