title: Final results of a randomised phase III study on adjuvant chemotherapy with 5 FU and levamisol in colon and rectum cancer stage II and III by the Norwegian Gastrointestinal Cancer Group.
abstract: BACKGROUND
  The recommendation of adjuvant chemotherapy for colon cancer with lymph node metastases, based on two studies from USA, was reluctantly accepted by Norwegian medical doctors. It was therefore decided to assess the role of adjuvant therapy with 5fluorouracil (5-FU) combined with levamisole (Lev) in a confirmatory randomised study.
  
  
  METHODS
  Four hundred and twenty five patients with operable colon and rectum cancer, Stage II and III (Dukes' stage B and C), were from January 1993 to October 1996, included in a randomised multicentre trial in Norway. The age limits were 18-75 years. Therapy started with a loading course of bolus i.v. 5-FU (450 mg/m(2)) daily for 5 days and p.o. doses of Lev (50 mg x 3) for 3 days. From day 28 a weekly i.v. 5-FU dose (450 mg/m(2)) were administered for 48 weeks. From day 28 also p.o. doses of Lev (50 mg x 3) for 3 days were given every 14 days. In total 214 patients were randomised to 5FU/Lev and 211 were included in the control group with surgery alone. Some did not comply with the inclusion and exclusion criteria, thus leaving 206 evaluable patients in each group.
  
  
  RESULTS
  There was no significant survival difference between the two groups at 5 years: Disease-free survival (DFS) was 73% after chemotherapy, 68% (p=0.24) in the control group, and corresponding cancer specific survival (CSS) 75% and 71%, respectively (p=0.69). There was no difference between the two groups when analysed for colon and rectum separately. However, the subgroup of colon cancer with stage III exhibited a statistically significant difference both for DFS, 58% vs. 37% (p=0.012) and CSS, 65% vs. 47% (p=0.032) in favour of adjuvant chemotherapy. The benefit was further statistically significant for women but not for men. Toxicity was generally mild and acceptable with no drug related fatalities.
  
  
  CONCLUSIONS
  Colon cancer patients with lymph node metastases benefit from adjuvant chemotherapy with 5-FU/Lev with acceptable toxicity. In a subgroup analysis females did better than males. Rectal cancer does not benefit from this regimen.
authors.affiliation: Olav Dahl, Section for Oncology, Institute of Medicine, University of Bergen, Norway. oldahl@online.no
authors.forename: Olav
authors.initials: O
authors.lastname: Dahl
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Fluge
authors.forename: Erik
authors.initials: E
authors.lastname: Carlsen
authors.forename: Johan N
authors.initials: JN
authors.lastname: Wiig
authors.forename: Helge E
authors.initials: HE
authors.lastname: Myrvold
authors.forename: Barthold
authors.initials: B
authors.lastname: Vonen
authors.forename: Nina
authors.initials: N
authors.lastname: Podhorny
authors.forename: Ottar
authors.initials: O
authors.lastname: Bjerkeset
authors.forename: Tor Jack
authors.initials: TJ
authors.lastname: Eide
authors.forename: Tore B
authors.initials: TB
authors.lastname: Halvorsen
authors.forename: Kjell Magne
authors.initials: KM
authors.lastname: Tveit
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007978:Levamisole / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009664:Norway; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D018501:Antirheumatic Agents; D007978:Levamisole; D005472:Fluorouracil