title: Unresectable colorectal liver metastases: the safety and efficacy of conversion therapy using hepatic arterial infusion immunochemotherapy with 5-fluorouracil and polyethylene glycol-interferon α-2a.
abstract: BACKGROUND
  Hepatic arterial infusion (HAI) or systemic chemotherapy has been used to treat unresectable colorectal liver metastases. The prognosis of the disease in recent years has been improved because chemotherapy is performed before hepatectomy to reduce tumor size (conversion therapy). The purpose of this study was to investigate the safety and efficacy of conversion therapy following HAI immunochemotherapy.
  
  
  METHODS
  Hepatic arterial infusion of 5-fluorouracil (5-FU)/polyethylene glycol (PEG)-IFNα-2a was performed in 21 patients. The primary endpoint was the safety of HAI and hepatectomy. The secondary endpoints were response rate, rate of conversion to hepatectomy, survival rate, and prognostic factors.
  
  
  RESULTS
  With regard to side effects, drugs were discontinued temporarily in one patient because of a decrease in white blood cell count; however, other patients continued chemotherapy. The response rate with HAI was 61.9 %, and the conversion rate was 38.1 %. Hepatectomy was completed successfully without mortality. Median progression-free survival (PFS) was 11.5 months (with and without conversion, 16.7 and 4.8 months, respectively; p = 0.021). Median overall survival was 34.6 months (with and without conversion, 48.4 and 26.6 months, respectively; p = 0.003). Prognosis was poor when the number of metastatic tumors was ≥10 [PFS: hazard ratio (HR) 32.21, p = 0.003; overall survival (OS): HR 9.13, p = 0.07], but prognosis improved after hepatectomy (OS: HR 0.08, p = 0.09).
  
  
  CONCLUSIONS
  Hepatic arterial infusion immunochemotherapy with 5-FU/PEG-IFNα-2a was performed safely without major side effects. Prognosis is expected to improve after successful conversion to hepatectomy.
authors.affiliation: Department of Surgery, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511 Osaka, Japan. nakai@surg.med.kindai.ac.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Nakai
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okuno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitaguchi
authors.forename: Hajime
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Yamasaki
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006498:Hepatectomy / Q000009:adverse effects; D006499:Hepatic Artery; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D007261:Infusions, Intra-Arterial; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a; D005472:Fluorouracil
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