title: Phase I/II study of radiologic hepatic arterial infusion of fluorouracil plus systemic irinotecan for unresectable hepatic metastases from colorectal cancer: Japan Clinical Oncology Group Trial 0208-DI.
abstract: OBJECTIVE
  Treatment of patients who have metastatic colorectal cancer (CRC) by using a combination of hepatic arterial infusion chemotherapy (HAIC) and systemic chemotherapy has resulted in promising clinical outcomes. Additionally, image-guided HAIC is reported to be less invasive and distribute drugs more accurately than surgical HAIC. The purpose of this study was to assess the combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan in a multicenter phase I/II study.
  
  
  METHODS
  Twenty-five patients with unresectable liver metastases from CRC were fitted with hepatic arterial catheter and port systems by using image-guided methods. Intraarterial fluorouracil (1,000 mg/m(2)) was administered on days 1, 8, and 15 of each treatment cycle. The dose of systemic irinotecan on days 1 and 15 was escalated from 75 mg/m(2).
  
  
  RESULTS
  No dose-limiting toxicity was encountered during phase I, and the recommended dose of irinotecan was set at 150 mg/m(2). Grade 3 or higher adverse events included hyperglycemia (15%), elevated γ-glutamyl transpeptidase levels (15%), and neutropenia (9%). The response rate and median survival time were 72% and 49.8 months (95% CI, 27.5-78.1 mo), respectively.
  
  
  CONCLUSIONS
  The combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan yielded favorable safety, response rate, and survival results. This combination should be evaluated in a large study.
authors.affiliation: Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan. arai-y3111@mvh.biglobe.ne.jp
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Arai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Yozo
authors.initials: Y
authors.lastname: Sato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aramaki
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Madoka
authors.initials: M
authors.lastname: Hamada
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Inaba
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Sojiro
authors.initials: S
authors.lastname: Morita
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Satake
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000401:mortality / Q000556:secondary*; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006499:Hepatic Artery / Q000000981:diagnostic imaging*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D000077146:Irinotecan; D007564:Japan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015641:Radiography, Interventional; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin