Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer

Ann Oncol. 2009 Sep;20(9):1529-1534. doi: 10.1093/annonc/mdp047. Epub 2009 May 27.

Abstract

Background: The REAL-2 and ML17032 trials demonstrated that the oral fluoropyrimidine, capecitabine, is noninferior to 5-fluorouracil (5-FU) for overall survival (OS) and progression-free survival (PFS), respectively, in advanced oesophago-gastric cancer.

Methods: Individual patient data were collected on all patients randomised within the trials (n = 1318). Kaplan-Meier survival curves were generated and the log-rank test was used to compare OS and PFS between patients receiving 5-FU combinations and capecitabine combinations. Stepwise multivariate Cox regression analysis was used to calculate corrected hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and PFS. Logistic regression was used for objective response rate. Forest plots with tests of heterogeneity were generated.

Results: OS was superior in the 654 patients treated with capecitabine combinations compared with the 664 patients treated with 5-FU combinations; HR 0.87 (95% CI 0.77-0.98, P = 0.02). Poor performance status, age <60 and metastatic disease were independent predictors of poor survival. There was no significant difference in PFS between treatment groups on multivariate analysis. Assessable patients treated with capecitabine combinations were significantly more likely to have an objective response to treatment than those treated with 5-FU combinations; odds ratio 1.38 (95% CI 1.10-1.73, P = 0.006).

Conclusion: OS is superior in patients treated with capecitabine combinations compared with 5-FU combinations in advanced oesophago-gastric cancer.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / mortality
  • Female
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / therapeutic use
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Treatment Outcome
  • Young Adult

Substances

  • Deoxycytidine
  • Capecitabine
  • Fluorouracil