title: Outcomes of a Phase I/II Trial of Hepatic Arterial Infusion of Oxaliplatin Combined with Intravenous 5-Fluorouracil and l-Leucovorin in Patients with Unresectable Liver Metastases from Colorectal Cancer After Systemic Chemotherapy Failure.
abstract: OBJECTIVE
  The purpose of this study was to assess hepatic arterial infusion (HAI) of oxaliplatin combined with intravenous 5-fluorouracil (5-FU) and l-leucovorin (l-LV) in colorectal cancer (CRC) patients with systemic chemotherapy failure in a phase I/II trial.
  
  
  METHODS
  CRC patients with unresectable liver metastases following standard systemic chemotherapy failure were eligible. A catheter-port system for HAI was placed using interventional radiology. In phase I, escalating doses of oxaliplatin for levels 1 and 2 were set at 50 and 100 mg/m2, respectively, and were combined with fixed doses of intravenous 5-FU (200 mg/m2bolus and 2400 mg/m2/46-h continuous infusion) and l-LV (200 mg/m2). The dose-limiting toxicity (DLT) was assessed, and the recommended dose (RD) was estimated. In phase II, patients receiving RD were included to assess the 6-month survival rate (the expected rate 80%), overall survival time, tumor response, and toxicity.
  
  
  RESULTS
  In phase I, none of the six enrolled patients exhibited DLT. RD for oxaliplatin by HAI was estimated as 100 mg/m2. In phase II, seven additional patients were enrolled. In patients receiving RD (n = 10), the disease control rates for total lesions and liver lesions were 30 and 70%, respectively. The 6-month survival rate and the overall survival time were 53.3% and 6.9 months, respectively. There were no adverse reactions equivalent to DLT in any of the patients.
  
  
  CONCLUSIONS
  The estimated RD for oxaliplatin by HAI in combination with intravenous 5-FU and l-LV was 100 mg/m2. This combination therapy was feasible and safe, but the expected efficacy was not achieved.
authors.affiliation: Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. ysato@aichi-cc.jp.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Inaba
authors.affiliation: Department of Medical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.affiliation: Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nishiofuku
authors.affiliation: Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Yamaura
authors.affiliation: Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Medical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahari
authors.affiliation: Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Medical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil
keywords: Colorectal cancer; Hepatic arterial infusion; Liver metastases; Oxaliplatin