title: A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: a Hellenic Cooperative Oncology Group study.
abstract: BACKGROUND
  Colon cancer is a public health problem worldwide. Adjuvant chemotherapy after surgical resection for stage III colon cancer has been shown to improve both progression-free and overall survival, and is currently recommended as standard therapy. However, its value for patients with stage II disease remains controversial. When this study was designed 5-fluorouracil (5FU) plus leucovorin (LV) was standard adjuvant treatment for colon cancer. Irinotecan (CPT-11) is a topoisomerase I inhibitor with activity in metastatic disease. In this multicenter adjuvant phase III trial, we evaluated the addition of irinotecan to weekly 5FU plus LV in patients with stage II or III colon cancer.
  
  
  METHODS
  The study included 873 eligible patients. The treatment consisted of weekly administration of irinotecan 80 mg/m2 intravenously (i.v.), LV 200 mg/m2 and 5FU 450 mg/m2 bolus (Arm A) versus LV 200 mg/m2 and 5FU 500 mg/m2 i.v. bolus (Arm B). In Arm A, treatments were administered weekly for four consecutive weeks, followed by a two-week rest, for a total of six cycles, while in Arm B treatments were administered weekly for six consecutive weeks, followed by a two-week rest, for a total of four cycles. The primary end-point was disease-free survival (DFS) at three years.
  
  
  RESULTS
  The probability of overall survival (OS) at three years was 0.88 for patients in Arm A and 0.86 for those in Arm B, while the five-year OS probability was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.436). Furthermore, the probability of DFS at three years was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.334). With the exception of leucopenia and neutropenia, which were higher in patients in Arm A, there were no significant differences in Grades 3 and 4 toxicities between the two regimens. The most frequently recorded Grade 3/4 toxicity was diarrhea in both treatment arms.
  
  
  CONCLUSIONS
  Irinotecan added to weekly bolus 5FU plus LV did not result in improvement in disease-free or overall survival in stage II or III colon cancer, but did increase toxicity.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry: ACTRN12610000148077.
authors.affiliation: Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Greece. chr_papadim@yahoo.gr
authors.forename: Christos A
authors.initials: CA
authors.lastname: Papadimitriou
authors.forename: Pavlos
authors.initials: P
authors.lastname: Papakostas
authors.forename: Maria
authors.initials: M
authors.lastname: Karina
authors.forename: Lia
authors.initials: L
authors.lastname: Malettou
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: Epaminontas
authors.initials: E
authors.lastname: Samantas
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Miliaras
authors.forename: George
authors.initials: G
authors.lastname: Basdanis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Xiros
authors.forename: George
authors.initials: G
authors.lastname: Klouvas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Bafaloukos
authors.forename: Georgia
authors.initials: G
authors.lastname: Kafiri
authors.forename: Irene
authors.initials: I
authors.lastname: Papaspirou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.forename: Charisios
authors.initials: C
authors.lastname: Karanikiotis
authors.forename: Theofanis
authors.initials: T
authors.lastname: Economopoulos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Efstratiou
authors.forename: Ippokratis
authors.initials: I
authors.lastname: Korantzis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pisanidis
authors.forename: Thomas
authors.initials: T
authors.lastname: Makatsoris
authors.forename: Fotini
authors.initials: F
authors.lastname: Matsiakou
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Aravantinos
authors.forename: Haralabos P
authors.initials: HP
authors.lastname: Kalofonos
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006115:Greece; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin