title: Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: a pooled analysis of randomized trials.
abstract: OBJECTIVE
  Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX.
  
  
  METHODS
  This analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients (FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate (RR), progression-free (PFS), overall survival (OS), and toxicity.
  
  
  RESULTS
  The fixed-effect pooled estimate for RR showed higher RR for FU-based regimens (Odds ratio [OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 (95% CI, 0.60 to 0.92; P = .007). However, for PFS (hazard ratio [HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS (HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities (thrombocytopenia-HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea-HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [HFS]-HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia (HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens.
  
  
  CONCLUSIONS
  The combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.
authors.affiliation: Drug Development Unit, Royal Marsden Hospital & Institute of Cancer Research, Downs Road, SM2 5PT Sutton, Surrey, United Kingdom. htarkenau@aol.com
authors.forename: Hendrik-Tobias
authors.initials: HT
authors.lastname: Arkenau
authors.forename: Dirk
authors.initials: D
authors.lastname: Arnold
authors.forename: Jim
authors.initials: J
authors.lastname: Cassidy
authors.forename: Eduardo
authors.initials: E
authors.lastname: Diaz-Rubio
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.forename: Howard
authors.initials: H
authors.lastname: Hochster
authors.forename: Andrea
authors.initials: A
authors.lastname: Martoni
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.forename: Axel
authors.initials: A
authors.lastname: Hinke
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schmoll
authors.forename: Rainer
authors.initials: R
authors.lastname: Porschen
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D014803:Vitamin B Complex / Q000008:administration & dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D014803:Vitamin B Complex; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil