title: Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial.
abstract: OBJECTIVE
  Although neoadjuvant chemoradiotherapy achieves low local recurrence rates in clinical stages II to III rectal cancer, it delays administration of optimal chemotherapy. We evaluated preoperative infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/bevacizumab with selective rather than consistent use of chemoradiotherapy.
  
  
  METHODS
  Thirty-two patients with clinical stages II to III rectal cancer participated in this single-center phase II trial. All were candidates for low anterior resection with total mesorectal excision (TME). Patients were to receive six cycles of FOLFOX, with bevacizumab included for cycles 1 to 4. Patients with stable/progressive disease were to have radiation before TME, whereas responders were to have immediate TME. Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX × 6 was recommended, but adjuvant regimens were left to clinician discretion. The primary outcome was R0 resection rate.
  
  
  RESULTS
  Between April 2007 and December 2008, 32 (100%) of 32 study participants had R0 resections. Two did not complete preoperative chemotherapy secondary to cardiovascular toxicity. Both had preoperative chemoradiotherapy and then R0 resections. Of 30 patients completing preoperative chemotherapy, all had tumor regression and TME without preoperative chemoradiotherapy. The pathologic complete response rate to chemotherapy alone was 8 of 32 (25%; 95% CI, 11% to 43%). The 4-year local recurrence rate was 0% (95% CI, 0% to 11%); the 4-year disease-free survival was 84% (95% CI, 67% to 94%).
  
  
  CONCLUSIONS
  For selected patients with clinical stages II to III rectal cancer, neoadjuvant chemotherapy and selective radiation does not seem to compromise outcomes. Preoperative Radiation or Selective Preoperative Radiation and Evaluation Before Chemotherapy and TME (PROSPECT), a randomized phase III trial to validate this experience, is now open in the US cooperative group network.
authors.affiliation: All authors: Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Deborah
authors.initials: D
authors.lastname: Schrag
authors.forename: Martin R
authors.initials: MR
authors.lastname: Weiser
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Goodman
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.forename: Ellen
authors.initials: E
authors.lastname: Hollywood
authors.forename: Andrea
authors.initials: A
authors.lastname: Cercek
authors.forename: Diane L
authors.initials: DL
authors.lastname: Reidy-Lagunes
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gollub
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.forename: Jose G
authors.initials: JG
authors.lastname: Guillem
authors.forename: Larissa K F
authors.initials: LK
authors.lastname: Temple
authors.forename: Philip B
authors.initials: PB
authors.lastname: Paty
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Saltz
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010865:Pilot Projects; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil