title: Phase I trial of hepatic arterial infusion (HAI) of floxuridine with modified oxaliplatin, 5-fluorouracil and leucovorin (m-FOLFOX6) in Chinese patients with unresectable liver metastases from colorectal cancer.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD) and preliminary efficacy of concurrent hepatic arterial infusion (HAI) of floxuridine (FUDR) and systemic modified oxaliplatin, 5-fluorouracil and leucovorin (m-FOLFOX6) in Chinese patients with unresectable hepatic metastases from colorectal cancer.
  
  
  METHODS
  Thirty-five patients with unresectable liver metastases with or without extrahepatic disease were treated with concurrent HAI and systemic m-FOLFOX6. HAI FUDR was delivered in a 14-day infusion with escalating dose levels, and each cycle was repeated every 4 weeks.
  
  
  RESULTS
  The MTD for FUDR was 0.12 mg/kg/day when combined with systemic m-FOLFOX6. The dose-limited toxicities were neutropenia (8.6 %), alanine aminotransferase/aspartate aminotransferase elevation (5.7 %) and diarrhea (11.4 %). The overall response rate was 68.6 % for hepatic metastases and 14.3 % for extrahepatic metastases. The median progression-free survival and overall survival were 8.23 and 25 months, respectively.
  
  
  CONCLUSIONS
  The recommended dose of FUDR was 0.12 mg/kg/day when combined with systemic m-FOLFOX6. This combination achieved a high response rate in hepatic disease and a high control rate in extrahepatic disease. Further study is needed to assess the potential additional value of HAI therapy in converting patients with hepatic metastases to candidates for resection.
authors.affiliation: Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.forename: Yangkui
authors.initials: Y
authors.lastname: Gu
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Yuan
authors.forename: Fenghua
authors.initials: F
authors.lastname: Wang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.forename: Huiyan
authors.initials: H
authors.lastname: Luo
authors.forename: Cui
authors.initials: C
authors.lastname: Chen
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: Peirong
authors.initials: P
authors.lastname: Ding
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wu
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Lu
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Pan
authors.forename: Ruihua
authors.initials: R
authors.lastname: Xu
authors.forename: Youjian
authors.initials: Y
authors.lastname: He
authors.forename: Desen
authors.initials: D
authors.lastname: Wan
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D002681:China; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000009:adverse effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D005467:Floxuridine; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil