title: A randomized phase II study to compare oxaliplatin plus 5-fluorouracil and leucovorin (FOLFOX4) versus oxaliplatin plus raltitrexed (TOMOX) as first-line chemotherapy for advanced colorectal cancer.
abstract: BACKGROUND
  The aim of this study was to compare TOMOX versus FOLFOX4 as first-line treatment of advanced colorectal cancer (CRC).
  
  
  METHODS
  191 chemotherapy-naïve patients were randomized to receive TOMOX or FOLFOX4. Patients were evaluated every 3 months and chemotherapy was continued until disease progression or unacceptable toxicity. Overall response rate was the primary endpoint.
  
  
  RESULTS
  183 patients were included in the intent-to-treat analysis (92 TOMOX and 91 FOLFOX4). Overall response rate was 45.6 and 36.3 % (p = 0.003) for TOMOX and FOLFOX4, respectively. No statistically significant differences were observed in overall survival (15.6 and 17.2 months; p = 0.475); progression-free survival (7.7 and 8.7 months; p = 0.292), and response duration (6.4 and 7.6 months; p = 0.372) for TOMOX and FOLFOX4, respectively. Grades 3 and 4 neutropenia (p < 0.0001) and leukopenia (p = 0.028) were more common with the FOLFOX4 regimen, while hepatic disorders and asthenia were higher in TOMOX group (p = ns). There were two treatment-related deaths in the FOLFOX4 arm and one in the TOMOX arm. Quality of life analysis based on the SF-36 revealed differences between the two regimens for physical and mental composite scores after 6 weeks, and for body pain and emotional role functioning after 6 and 12 weeks; all of these favored the FOLFOX4 arm (p ≤ 0.05).
  
  
  CONCLUSIONS
  TOMOX and FOLFOX4 seem to have similar efficacy and are well tolerated in the first-line treatment for advanced CRC with different profiles of toxicity. The convenient TOMOX regimen may offer an alternative to fluoropyrimidine-based regimens.
authors.affiliation: Medical Oncology Department, University Hospital 12 de Octubre, Madrid, Spain. cgravalos@telefonica.net
authors.forename: Cristina
authors.initials: C
authors.lastname: Gravalos
authors.forename: Antonieta
authors.initials: A
authors.lastname: Salut
authors.forename: Carlos
authors.initials: C
authors.lastname: García-Girón
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Carbonero
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: León
authors.forename: Isabel
authors.initials: I
authors.lastname: Sevilla
authors.forename: Joan
authors.initials: J
authors.lastname: Maurel
authors.forename: Beatriz
authors.initials: B
authors.lastname: Esteban
authors.forename: Eduardo
authors.initials: E
authors.lastname: García-Rico
authors.forename: Adolfo
authors.initials: A
authors.lastname: Murias
authors.forename: Hernán
authors.initials: H
authors.lastname: Cortés-Funes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage; D013876:Thiophenes / Q000008:administration & dosage
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; C068874:raltitrexed; D002955:Leucovorin; D005472:Fluorouracil