title: Hepatic artery infusion therapy is effective for chemotherapy-resistant liver metastatic colorectal cancer.
abstract: BACKGROUND
  Systemic FOLFOX (folinic acid (leucovorin (LV)), 5-fluorouracil (5-FU), and oxaliplatin), FOLFIRI (LV, 5-FU, and irinotecan), or FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) chemotherapy regimens and additional molecular-target treatments, including anti-vascular endothelial growth factor, anti-epidermal growth factor receptor, and anti-multi-kinase antibodies, have been recommended for unresectable recurrent colorectal cancers. However, no effective treatments are currently available for cases refractory to these therapies. Therefore, the development of alternative therapies is desired. In the present study, we administered and observed the effectiveness of hepatic artery infusion therapy (HAIC) in patients with unresectable liver metastatic colorectal cancers refractory to systemic chemotherapy. In addition, we observed that in an experimental system with anticancer drug-resistant colorectal cancer lines, apoptosis and cell death could be induced by increasing anticancer drug concentrations.
  
  
  METHODS
  The subjects had liver metastatic colorectal cancers that were unresponsive to systemic chemotherapy (FOLFOX/FOLFIRI) or to additional molecular-target therapies for progressive disease. Hepatic infusion tube placement was conducted according to the Seldinger method to insert a catheter with a side hole via the right femoral artery. A coiling procedure was performed to prevent drug influx into the gastroduodenal artery. Ten subjects were selected, and the results were evaluated after HAIC (5-FU and LV administered once weekly). Moreover, anticancer drug-resistant colorectal cancer lines were subsequently prepared to investigate whether increased anticancer drug concentrations could induce apoptosis or cell death.
  
  
  RESULTS
  Of the 10 subjects, 3 (30 %) showed partial response and 4 (40 %) showed no change according to computed tomography imaging findings obtained after hepatic artery infusion. The disease control rate was 70 %. Eight subjects had improved quality of life. Survival time ranged from 2 to 16 months (median, 9 months). Meanwhile, we found that higher anticancer drug concentrations induced apoptosis and cell death in an anticancer drug-resistant colorectal cancer cell line.
  
  
  CONCLUSIONS
  HAIC was effective in some systemic chemotherapy-resistant colorectal cancers with liver metastases and should be considered as an effective palliative therapy. This supports the finding that apoptosis and cell death could be induced in anticancer drug-resistant colorectal cancer cells in a drug concentration-dependent manner.
authors.affiliation: First Department of Surgery, University of Fukui, 23-3, Eiheiji-cho, Yoshida-gun, Fukui, 9101193, Japan. tgoi@u-fukui.ac.jp.
authors.forename: Takanori
authors.initials: T
authors.lastname: Goi
authors.affiliation: First Department of Surgery, University of Fukui, 23-3, Eiheiji-cho, Yoshida-gun, Fukui, 9101193, Japan. naruse@u-fukui.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Naruse
authors.affiliation: First Department of Surgery, University of Fukui, 23-3, Eiheiji-cho, Yoshida-gun, Fukui, 9101193, Japan. kimtann123@hotmail.com.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: First Department of Surgery, University of Fukui, 23-3, Eiheiji-cho, Yoshida-gun, Fukui, 9101193, Japan. fujimoto@u-fukui.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujimoto
authors.affiliation: First Department of Surgery, University of Fukui, 23-3, Eiheiji-cho, Yoshida-gun, Fukui, 9101193, Japan. mmitsu@u-fukui.ac.jp.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Morikawa
authors.affiliation: First Department of Surgery, University of Fukui, 23-3, Eiheiji-cho, Yoshida-gun, Fukui, 9101193, Japan. koneri@u-fukui.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Koneri
authors.affiliation: First Department of Surgery, University of Fukui, 23-3, Eiheiji-cho, Yoshida-gun, Fukui, 9101193, Japan. akio@u-fukui.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Yamaguchi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005472:Fluorouracil