title: Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure.
abstract: BACKGROUND
  We have previously shown promising activity of hepatic arterial infusion (HAI) oxaliplatin combined with intravenous (IV) 5-fluorouracil (5-FU) and leucovorin (LV) as first-line chemotherapy in patients with colorectal liver metastases (CRLM) (intent-to-treat [ITT] objective response rate [ORR], 64%; secondary resection rate, 18%; overall survival [OS], 27 months). Whether this regimen could be beneficial after systemic chemotherapy failure is unknown.
  
  
  METHODS
  Patients with unresectable CRLM and history of systemic chemotherapy failure were treated bimonthly with HAI oxaliplatin (100 mg/m(2) 2 hours) combined with IV LV and IV bolus and infusional 5FU (modified LV5FU2 regimen).
  
  
  RESULTS
  Forty-four consecutive patients (median age 56 years; median number of prior systemic chemotherapy regimens, 2 range 1-5) were included, of whom 43 (98%) had previously received oxaliplatin (n = 34), irinotecan (n = 37), or both (n = 28). Patients received a median of nine cycles of HAI oxaliplatin and IV modified LV5FU2 (range 0-25). Toxicity included grade 3-4 neutropenia (43%), grade 2-3 neuropathy (43%), and grade 3-4 abdominal pain (14%). We observed 24 partial ORs (62%) among the 39 assessable patients (ITT ORR, 55%; 95% CI, 40-69%), including 17, 12, and 12 patients who had failed to respond to prior systemic chemotherapy with FOLFIRI, FOLFOX, or both, respectively. Tumor response allowed further R0 surgical resection (n = 7) or radiofrequency ablation (n = 1) of initially unresectable CRLM in eight patients (18%). Median progression-free survival and OS were 7 and 16 months, respectively.
  
  
  CONCLUSIONS
  HAI oxaliplatin and IV LV5FU2 is feasible, safe, and shows promising activity after systemic chemotherapy failure, allowing surgical resection of initially unresectable CRLM in 18% of patients.
authors: Department of Medicine, Institut Gustave Roussy, Villejuif, France.
authors: Valérie
authors: V
authors: Boige
authors: David
authors: D
authors: Malka
authors: Dominique
authors: D
authors: Elias
authors: Marine
authors: M
authors: Castaing
authors: Thierry
authors: T
authors: De Baere
authors: Diane
authors: D
authors: Goere
authors: Clarisse
authors: C
authors: Dromain
authors: Marc
authors: M
authors: Pocard
authors: Michel
authors: M
authors: Ducreux
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; 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; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil