title: Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer.
abstract: OBJECTIVE
  We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer.
  
  
  METHODS
  A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU.
  
  
  RESULTS
  The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%).
  
  
  CONCLUSIONS
  Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Minsky
authors.forename: A M
authors.initials: AM
authors.lastname: Cohen
authors.forename: W E
authors.initials: WE
authors.lastname: Enker
authors.forename: L
authors.initials: L
authors.lastname: Saltz
authors.forename: J G
authors.initials: JG
authors.lastname: Guillem
authors.forename: P B
authors.initials: PB
authors.lastname: Paty
authors.forename: D P
authors.initials: DP
authors.lastname: Kelsen
authors.forename: N
authors.initials: N
authors.lastname: Kemeny
authors.forename: D
authors.initials: D
authors.lastname: Ilson
authors.forename: J
authors.initials: J
authors.lastname: Bass
authors.forename: J
authors.initials: J
authors.lastname: Conti
mesh_terms: D000328:Adult; D000368:Aged; D000931:Antidotes / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil