Capecitabine and oxaliplatin for advanced esophagogastric cancer.
BACKGROUND
We evaluated capecitabine (an oral fluoropyrimidine) and oxaliplatin (a platinum compound) as alternatives to infused fluorouracil and cisplatin, respectively, for untreated advanced esophagogastric cancer.


METHODS
In a two-by-two design, we randomly assigned 1002 patients to receive triplet therapy with epirubicin and cisplatin plus either fluorouracil (ECF) or capecitabine (ECX) or triplet therapy with epirubicin and oxaliplatin plus either fluorouracil (EOF) or capecitabine (EOX). The primary end point was noninferiority in overall survival for the triplet therapies containing capecitabine as compared with fluorouracil and for those containing oxaliplatin as compared with cisplatin.


RESULTS
For the capecitabine-fluorouracil comparison, the hazard ratio for death in the capecitabine group was 0.86 (95% confidence interval [CI], 0.80 to 0.99); for the oxaliplatin-cisplatin comparison, the hazard ratio for the oxaliplatin group was 0.92 (95% CI, 0.80 to 1.10). The upper limit of the confidence intervals for both hazard ratios excluded the predefined noninferiority margin of 1.23. Median survival times in the ECF, ECX, EOF, and EOX groups were 9.9 months, 9.9 months, 9.3 months, and 11.2 months, respectively; survival rates at 1 year were 37.7%, 40.8%, 40.4%, and 46.8%, respectively. In the secondary analysis, overall survival was longer with EOX than with ECF, with a hazard ratio for death of 0.80 in the EOX group (95% CI, 0.66 to 0.97; P=0.02). Progression-free survival and response rates did not differ significantly among the regimens. Toxic effects of capecitabine and fluorouracil were similar. As compared with cisplatin, oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia, alopecia, renal toxicity, and thromboembolism but with slightly higher incidences of grade 3 or 4 diarrhea and neuropathy.


CONCLUSIONS
Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer. (Current Controlled Trials number, ISRCTN51678883 [controlled-trials.com].).
Cunningham
David
D
Royal Marsden Hospital National Health Service Foundation Trust, Surrey and London, United Kingdom.
Starling
Naureen
N
Rao
Sheela
S
Iveson
Timothy
T
Nicolson
Marianne
M
Coxon
Fareeda
F
Middleton
Gary
G
Daniel
Francis
F
Oates
Jacqueline
J
Norman
Andrew Richard
AR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D016016:Proportional Hazards Models; D011788:Quality of Life; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D015251:Epirubicin; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil