title: Capecitabine plus Irinotecan (XELIRI regimen) compared to 5-FU/LV plus Irinotecan (FOLFIRI regimen) as neoadjuvant treatment for patients with unresectable liver-only metastases of metastatic colorectal cancer: a randomised prospective phase II trial.
abstract: BACKGROUND
  Phase II studies have shown that the combination of capecitabine and irinotecan (the XELIRI regimen) is active in metastatic colorectal cancer (MCRC). There are, however, no data about the use of the XELIRI regimen in the neoadjuvant treatment.
  
  
  METHODS
  Patients with unresectable liver-only metastases of MCRC with < or = 75 years of age were randomised to either the XELIRI (irinotecan 250 mg/m(2) given on day one and capecitabine 1000 mg/m(2) twice daily from day 2-15, every 21 days) or the FOLFIRI arm (irinotecan 180 mg/m(2), 5-FU 400 mg/m(2), LV 200 mg/m(2), 5-FU 2400 mg/m(2) (46-h infusion)--all given on day one, every 14 days). Primary end points were objective response rate (ORR) and rate of radical (R0) surgical resection. Secondary end points were progression-free survival (PFS), overall survival (OS) and safety.
  
  
  RESULTS
  Altogether 87 patients were enrolled (41 pts in the XELIRI and 46 pts in the FOLFIRI arm). The median age was 63 years (63 years in the XELIRI and 62 years in the FOLFIRI arm) (p = 0.33). ORR was 49% in the XELIRI and 48% in the FOLFIRI arm (p = 0.76). The rate of radical R0 resection was 24% in both arms of patients. At the end of treatment, 37% of patients in the XELIRI and 26% of patients in the FOLFIRI arm were without evidence of the disease (CR+R0 resection) (p = 0.56). There were no statistical differences in grade 3 or 4 adverse events between both arms: diarrhoea 7% vs. 6%, neutropenia 5% vs. 13%, ischemic stroke 0 vs. 2%, acute coronary syndrome 2% vs. 4%, respectively. At the median follow up of 17 (range 1-39) months, the median PFS was 10.3 months in the XELIRI and 9.3 months in the FOLFIRI arm (p = 0.78), the median OS was 30.7 months in the XELIRI arm and 16.6 months in the FOLFIRI arm (p = 0.16).
  
  
  CONCLUSIONS
  The XELIRI regimen showed similar ORR as the FOLFIRI regimen in the neoadjuvant treatment of patients with MCRC. In addition, the XELIRI regimen showed similar PFS and OS with acceptable toxicity compared to the FOLFIRI regimen.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN19912492.
authors.affiliation: Institute of Oncology, Division of Medical Oncology, Zaloska 2, 1000 Ljubljana, Slovenia. eskof@onko-i.si
authors.forename: Erik
authors.initials: E
authors.lastname: Skof
authors.forename: Martina
authors.initials: M
authors.lastname: Rebersek
authors.forename: Zvezdana
authors.initials: Z
authors.lastname: Hlebanja
authors.forename: Janja
authors.initials: J
authors.lastname: Ocvirk
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D020360:Neoadjuvant Therapy; D009503:Neutropenia / Q000139:chemically induced; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin