title: No benefit of adjuvant Fluorouracil Leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): Long term results of a randomized trial (I-CNR-RT).
abstract: OBJECTIVE
  To evaluate the effect of adjuvant chemotherapy (ACT) in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiation (NACT-RT). The study was funded by the Italian National Research Council (CNR).
  
  
  METHODS
  From September 1992 to January 2001, 655 patients with LARC (clinically T3-4, any N) treated with NACT-RT and surgery, were randomized in two arms: follow-up (Arm A) or 6 cycles of ACT with 5 fluorouracil (5FU)-Folinic Acid (Arm B). NACT-RT consisted of 45Gy/28/ff concurrent with 5FU (350mg/sqm) and Folinic Acid (20mg/sqm) on days 1-5 and 29-33; surgery was performed after 4-6weeks. Median follow up was 63·7months. Primary end point was overall survival (OS).
  
  
  RESULTS
  634/655 patients were evaluable (Arm A 310, Arm B 324); 92·5% of Arm A and 91% of Arm B patients received the preoperative treatment as in the protocol; 294 patients of Arm A (94·8%) and 296 of Arm B (91·3%) underwent a radical resection; complete pathologic response and overall downstaging rates did not show any significant difference in the two arms. 83/297 (28%) patients in Arm B, never started ACT. Five year OS and DFS did not show any significant difference in the two treatment arms. Distant metastases occurred in 62 patients (21%) in Arm A and in 58 (19·6%) in Arm B.
  
  
  CONCLUSIONS
  In patients with LARC treated with NACT-RT, the addition of ACT did not improve 5year OS and DFS and had no impact on the distant metastasis rate.
authors.affiliation: Department of Radiotherapy, Pisa University, Italy. Electronic address: a.sainato@ao-pisa.toscana.it.
authors.forename: Aldo
authors.initials: A
authors.lastname: Sainato
authors.affiliation: Department of Radiotherapy, Pisa University, Italy. Electronic address: magnolia720@hotmail.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cernusco Luna Nunzia
authors.affiliation: Cattedra di radioterapia, Università Cattolica S. Cuore, Rome, Italy. Electronic address: vvalentini@rm.unicatt.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.affiliation: Oncology Referral Center, National Cancer Institute, Aviano, Italy. Electronic address: adepaoli@cro.it.
authors.forename: Antonino
authors.initials: A
authors.lastname: De Paoli
authors.affiliation: Department of Radiotherapy, "La Sapienza University", Rome, Italy. Electronic address: Riccardo.Maurizienrici@uniroma1.it.
authors.forename: Enrici Riccardo
authors.initials: ER
authors.lastname: Maurizi
authors.affiliation: Department of Radiotherapy, Perugia University, Italy. Electronic address: kiralupis@libero.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Lupattelli
authors.affiliation: Department of Radiotherapy, Perugia University, Italy. Electronic address: cynthia.aristei@unipg.it.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Aristei
authors.affiliation: Department of Radiotherapy, Trieste University, Italy. Electronic address: cristiana.vidali@libero.it.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Vidali
authors.affiliation: Department of Radiotherapy, Hospital of Venice, Italy. Electronic address: monica.conti@ulss12.ve.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Conti
authors.affiliation: Department of Radiotherapy, Florence University, Italy. Electronic address: alessandragalardi@hotmail.com.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Galardi
authors.affiliation: Department of Radiotherapy, Hospital of Arezzo, Italy. Electronic address: p.ponticelli@usl8.toscana.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ponticelli
authors.affiliation: Oncological Institute of Veneto, Padova, Italy. Electronic address: marialuisa.friso@ioveneto.it.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Friso
authors.affiliation: Department of Radiotherapy, Hospital of Belluno, Italy. Electronic address: tiziana.iannone@ulss.belluno.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Iannone
authors.affiliation: Department of Radiotherapy, "La Sapienza University", Rome, Italy. Electronic address: mattiafosti@gmail.com.
authors.forename: Falchetto Mattia
authors.initials: FM
authors.lastname: Osti
authors.affiliation: Department of Radiotherapy, Pisa University, Italy. Electronic address: b.manfredi@ao-pisa.toscana.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Manfredi
authors.affiliation: Department of Radiotherapy, "Centro Oncologico Fiorentino", Sesto Fiorentino, Italy. Electronic address: marianna-c@hotmail.it.
authors.forename: Marianna
authors.initials: M
authors.lastname: Coppola
authors.affiliation: Department of Medical Oncology, Pisa University, Italy. Electronic address: c.orlandini@med.unipi.it.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Orlandini
authors.affiliation: Department of Radiotherapy, "Centro Oncologico Fiorentino", Sesto Fiorentino, Italy. Electronic address: lcionini@tin.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Cionini
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D002955:Leucovorin; D005472:Fluorouracil
keywords: Adjuvant chemotherapy; Preoperative radiochemotherapy; Rectal cancer