title: Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: Results from the randomised phase III Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1).
abstract: OBJECTIVE
  PETACC-1 assessed if raltitrexed is non-inferior to 5-fluorouracil and leucovorin for relapse-free survival (RFS) and overall survival (OS) in adjuvant stage III colon cancer.
  
  
  METHODS
  Non-inferiority required both HR for RFS and OS<1.25 at 1-sided alpha=0.05. Patients (1921) were randomised to six cycles of 5-FU/LV (n=969) or eight cycles of raltitrexed (n=952). We report the final results in 993 eligible patients who started and completed the allocated treatment (489 5-FU/LV and n=504 Raltitrexed) of whom respectively 146 and 148 died, respectively.
  
  
  RESULTS
  The trial closed prematurely when 17 (1.9%) raltitrexed-related deaths were reported. Haematological and gastrointestinal toxicities were more frequent with 5-FU/LV, liver toxicities with raltitrexed. Raltitrexed was stopped for toxicity in 13.2% and 5-FU/LV in 8.5%. Sixty-day mortality was 9% versus 7%. With 4.1 years median follow-up, the HR for RFS was 1.16 (90% CI 0.99-1.37) and that for OS was 1.01 (90% CI 0.84-1.23).
  
  
  CONCLUSIONS
  The trial failed to demonstrate non-inferiority of raltitrexed.
  
  
  BACKGROUND
  Free drugs and financial support from AstraZeneca.
authors: Institute of Oncology and Radiology, Clinic for Medical Oncology, Pasterova 14, 11000 Belgrade, Serbia. ipopov@ncrc.ac.yu
authors: Ivan
authors: I
authors: Popov
authors: Alfredo
authors: A
authors: Carrato
authors: Alberto
authors: A
authors: Sobrero
authors: Mark
authors: M
authors: Vincent
authors: David
authors: D
authors: Kerr
authors: Roberto
authors: R
authors: Labianca
authors: Angelo
authors: A
authors: Raffaele Bianco
authors: Mostafa
authors: M
authors: El-Serafi
authors: Laurent
authors: L
authors: Bedenne
authors: Bernard
authors: B
authors: Paillot
authors: Enrico
authors: E
authors: Mini
authors: Evaristo
authors: E
authors: Sanches
authors: John
authors: J
authors: Welch
authors: Laurence
authors: L
authors: Collette
authors: Michel
authors: M
authors: Praet
authors: Jacques
authors: J
authors: Wils
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D013876:Thiophenes; C068874:raltitrexed; D002955:Leucovorin; D005472:Fluorouracil