title: Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial.
abstract: OBJECTIVE
  Concomitant radiochemotherapy (RCT) is the standard for locally advanced anal canal carcinoma (LAACC). Questions regarding the role of induction chemotherapy (ICT) and a higher radiation dose in LAACC are pending. Our trial was designed to determine whether dose escalation of the radiation boost or two cycles of ICT before concomitant RCT lead to an improvement in colostomy-free survival (CFS).
  
  
  METHODS
  Patients with tumors ≥ 40 mm, or < 40 mm and N1-3M0 were randomly assigned to one of four treatment arms: (A) two ICT cycles (fluorouracil 800 mg/m(2)/d intravenous [IV] infusion, days 1 through 4 and 29 to 32; and cisplatin 80 mg/m(2) IV, on days 1 and 29), RCT (45 Gy in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), and standard-dose boost (SD; 15 Gy); (B) two ICT cycles, RCT, and high-dose boost (HD; 20-25 Gy); (C): RCT and SD boost (reference arm); and (D) RCT and HD boost.
  
  
  RESULTS
  Two hundred eighty-three of 307 patients achieved full treatment. With a median follow-up period of 50 months, the 5-year CFS rates were 69.6%, 82.4%, 77.1%, and 72.7% in arms A, B, C, and D, respectively. Considering the 2 × 2 factorial analysis, the 5-year CFS was 76.5% versus 75.0% (P = .37) in groups A and B versus C and D, respectively (ICT effect), and 73.7% versus 77.8% in groups A and C versus B and D, respectively (RT-dose effect; P = .067).
  
  
  CONCLUSIONS
  Using CFS as our main end point, we did not find an advantage for either ICT or HD radiation boost in LAACC. Nevertheless, the results of the most treatment-intense arm B should prompt the design of further intensification studies.
authors.affiliation: EA 4360Centre, Alexis Vautrin and Nancy University,Vandoeuvre-lès-Nancy, France. d.peiffert@nancy.unicancer.fr
authors.forename: Didier
authors.initials: D
authors.lastname: Peiffert
authors.forename: Laetitia
authors.initials: L
authors.lastname: Tournier-Rangeard
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gérard
authors.forename: Claire
authors.initials: C
authors.lastname: Lemanski
authors.forename: Eric
authors.initials: E
authors.lastname: François
authors.forename: Marc
authors.initials: M
authors.lastname: Giovannini
authors.forename: Frédérique
authors.initials: F
authors.lastname: Cvitkovic
authors.forename: Xavier
authors.initials: X
authors.lastname: Mirabel
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Luporsi
authors.forename: Thierry
authors.initials: T
authors.lastname: Conroy
authors.forename: Christine
authors.initials: C
authors.lastname: Montoto-Grillot
authors.forename: Françoise
authors.initials: F
authors.lastname: Mornex
authors.forename: Antoine
authors.initials: A
authors.lastname: Lusinchi
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Hannoun-Lévi
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Seitz
authors.forename: Antoine
authors.initials: A
authors.lastname: Adenis
authors.forename: Christophe
authors.initials: C
authors.lastname: Hennequin
authors.forename: Bernard
authors.initials: B
authors.lastname: Denis
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
mesh_terms: D000328:Adult; D000368:Aged; D001003:Anal Canal; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage
chemical_list: D002945:Cisplatin