title: Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114.
abstract: OBJECTIVE
  The combination of radiation therapy with fluorouracil (5-FU)-based chemotherapy is generally accepted as appropriate postoperative therapy for patients with adenocarcinomas of the rectum that extend through the bowel wall or with lymph nodes positive for tumor. We attempted to determine whether the efficacy of this postoperative therapy could be improved by the addition of leucovorin and/or levamisole.
  
  
  METHODS
  A total of 1,696 patients were randomized and eligible for treatment with one of four treatment schemes. All patients received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic radiation therapy with chemotherapy and two more cycles of the same systemic chemotherapy. Chemotherapy was either 5-FU alone, 5-FU with leucovorin, 5-FU with levamisole, or 5-FU with leucovorin and levamisole.
  
  
  RESULTS
  With a median follow-up duration of 48 months, there is no statistically significant advantage to any of the treatment regimens compared with bolus 5-FU alone. There is evidence of increased gastrointestinal toxicity with the three-drug combination compared with bolus 5-FU alone. Statistical analysis suggests it is very unlikely that either levamisole-containing combination will be shown to be of value with further follow-up evaluation.
  
  
  CONCLUSIONS
  There is no evidence at present for a beneficial effect of levamisole in the adjuvant treatment of rectal cancer. Definitive evaluation of the effect of the addition of leucovorin to 5-FU and pelvic radiation will require further follow-up evaluation.
authors.affiliation: Department of Radiation Oncology, University of North Carolina at Chapel Hill, School of Medicine 27599-7512, USA. tepper@radonc.unc.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Tepper
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: G R
authors.initials: GR
authors.lastname: Petroni
authors.forename: D
authors.initials: D
authors.lastname: Hollis
authors.forename: E
authors.initials: E
authors.lastname: Cooke
authors.forename: A B
authors.initials: AB
authors.lastname: Benson
authors.forename: B
authors.initials: B
authors.lastname: Cummings
authors.forename: L L
authors.initials: LL
authors.lastname: Gunderson
authors.forename: J S
authors.initials: JS
authors.lastname: Macdonald
authors.forename: J A
authors.initials: JA
authors.lastname: Martenson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000209:etiology; D000931:Antidotes / Q000008:administration & dosage / Q000009:adverse effects; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D002423:Cause of Death; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000209:etiology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D007970:Leukopenia / Q000209:etiology; D007978:Levamisole / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D007978:Levamisole; D002955:Leucovorin; D005472:Fluorouracil