title: Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144.
abstract: OBJECTIVE
  Adjuvant chemoradiotherapy after or before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. We studied three postoperative fluorouracil (FU) radiochemotherapy regimens.
  
  
  METHODS
  After resection of T3-4, N0, M0 or T1-4, N1, 2M0 rectal adenocarcinoma, 1,917 patients were randomly assigned to arm 1, with bolus FU in two 5-day cycles every 28 days before and after radiotherapy (XRT) plus FU via protracted venous infusion (PVI) 225 mg/m2/d during XRT; arm 2 (PVI-only arm), with PVI 42 days before and 56 days after XRT + PVI; or arm 3 (bolus-only arm), with bolus FU + leucovorin (LV) in two 5-day cycles before and after XRT, plus bolus FU + LV (levamisole was administered each cycle before and after XRT). Patients were stratified by operation type, T and N stage, and time from surgery.
  
  
  RESULTS
  Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 49% to 55% of the bolus arms versus 4% in the PVI arm. No disease-free survival (DFS) or OS difference was detected (3-year DFS, 67% to 69% and 3-year OS, 81% to 83% in all arms). Locoregional failure (LRF) at first relapse was 8% in arm 1, 4.6% in arm 2, and 7% in arm 3. LRF in T1-2, N1-2, and T3, N0-2 primaries who received low anterior resection (those most suitable for primary resection) was 5% in arm 1, 3% in arm 2, and 5% in arm 3.
  
  
  CONCLUSIONS
  All arms provide similar relapse-free survival and OS, with different toxicity profiles and central catheter requirements. LRF with postoperative therapy is low, justifying initial resection for T1-2, N0-2 and T3, and N0-2 anterior resection candidates.
authors.affiliation: Kansas City Community Clinical Oncology Program (CCOP), Kansas City, KS, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Smalley
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Benedetti
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Williamson
authors.forename: John M
authors.initials: JM
authors.lastname: Robertson
authors.forename: Norman C
authors.initials: NC
authors.lastname: Estes
authors.forename: Tracy
authors.initials: T
authors.lastname: Maher
authors.forename: Barbara
authors.initials: B
authors.lastname: Fisher
authors.forename: Tyvin A
authors.initials: TA
authors.lastname: Rich
authors.forename: James A
authors.initials: JA
authors.lastname: Martenson
authors.forename: John W
authors.initials: JW
authors.lastname: Kugler
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Haller
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mayer
authors.forename: James N
authors.initials: JN
authors.lastname: Atkins
authors.forename: Christine
authors.initials: C
authors.lastname: Cripps
authors.forename: John
authors.initials: J
authors.lastname: Pedersen
authors.forename: Phillip O
authors.initials: PO
authors.lastname: Periman
authors.forename: Michael S
authors.initials: MS
authors.lastname: Tanaka
authors.forename: Cynthia G
authors.initials: CG
authors.lastname: Leichman
authors.forename: John S
authors.initials: JS
authors.lastname: Macdonald
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D007978:Levamisole / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007978:Levamisole; D002955:Leucovorin; D005472:Fluorouracil