title: Neoadjuvant treatment with weekly high-dose 5-Fluorouracil as 24-hour infusion, folinic acid and oxaliplatin in patients with primary resectable liver metastases of colorectal cancer.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of neoadjuvant treatment comprising weekly high-dose 5-fluorouracil (5-FU) as a 24-hour infusion, folinic acid (FA) and biweekly oxaliplatin (L-OHP), followed by metastatic resection in patients with primarily resectable liver metastases of colorectal cancer (CRC).
  
  
  METHODS
  20 patients with primarily resectable liver metastases of CRC were enrolled in a prospective phase II study. On an outpatient basis, the patients received a treatment regimen comprising biweekly 85 mg/m(2) L-OHP in the form of a 2-hour intravenous infusion and 500 mg/m(2) FA as a 1- to 2-hour intravenous infusion, followed by 2,600 mg/m(2 ) 5-FU administered as a 24-hour intravenous infusion once weekly. A single treatment cycle comprised one infusion per week during a period of 6 weeks followed by a 2-week rest. Two cycles were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted, and the patients were followed up.
  
  
  RESULTS
  After neoadjuvant therapy, 2 of the original 20 patients showed complete remission (CR; 10%) and 18 patients partial remission (PR; 90%). As the main symptom of toxicity, diarrhea (CTC toxicity grade 3-4) was observed in 6 patients (30%), followed by vomiting in 3 patients (15%). The curative resectability rate was 80% (16 of 20). In 9 of 18 patients (50%) undergoing surgical intervention, mild postoperative complications, mainly wound healing disturbances (n = 5), occurred. No postoperative mortality was observed. Over a median follow-up of 23 months (12-38) 6 of 16 curatively resected patients developed distant metastases and 1 patient a local pelvic recurrence. The 2-year disease-free survival rate was 52% and the 2-year cancer-related survival rate 80%.
  
  
  CONCLUSIONS
  The neoadjuvant treatment with weekly high-dose 5-FU in the form of a 24-hour infusion combined with FA and L-OHP is very effective and well tolerated. Surgical morbidity does not appear to be increased by the neoadjuvant treatment.
authors.affiliation: Department of Internal Medicine I, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany. Axel.Wein@med1.imed.uni-erlangen.de
authors.forename: A
authors.initials: A
authors.lastname: Wein
authors.forename: C
authors.initials: C
authors.lastname: Riedel
authors.forename: W
authors.initials: W
authors.lastname: Brückl
authors.forename: S
authors.initials: S
authors.lastname: Merkel
authors.forename: R
authors.initials: R
authors.lastname: Ott
authors.forename: B
authors.initials: B
authors.lastname: Hanke
authors.forename: U
authors.initials: U
authors.lastname: Baum
authors.forename: F
authors.initials: F
authors.lastname: Fuchs
authors.forename: K
authors.initials: K
authors.lastname: Günther
authors.forename: T
authors.initials: T
authors.lastname: Reck
authors.forename: T
authors.initials: T
authors.lastname: Papadopoulos
authors.forename: E G
authors.initials: EG
authors.lastname: Hahn
authors.forename: W
authors.initials: W
authors.lastname: Hohenberger
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil