Correspondence

Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer

N Engl J Med 2010; 362:858-859March 4, 2010

Article

To the Editor:

We reported previously (Jan. 3, 2008, issue)1 that capecitabine and oxaliplatin are as effective as infused fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer that was inoperable and either locally advanced or metastatic. The median survival was 11.2 months among the patients treated with epirubicin, oxaliplatin, and capecitabine (EOC [called EOX in the 2008 article]) and 9.9 months among the patients treated with epirubicin, cisplatin, and fluorouracil (ECF) (hazard ratio for death in the EOC group vs. the ECF group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02).

The per-protocol population of 964 patients consisted of 269 with locally advanced disease and 695 with metastatic disease. In a retrospective analysis of these two groups, the median survival among patients with locally advanced disease was 14.0 months (95% CI, 12.5 to 15.4) as compared with 9.3 months (95% CI, 8.6 to 9.9 months) among patients with metastatic disease (Figure 1AFigure 1Kaplan–Meier Estimates of Overall Survival in the Per-Protocol Population.). This survival difference is significant (hazard ratio for death from metastatic vs. locally advanced disease, 1.54; 95% CI, 1.34 to 1.78; P<0.001).

The longer median survival among patients with locally advanced disease than among those with metastatic disease is not an unexpected finding. The presence of liver peritoneal metastases have previously been noted to be independent predictors of poor prognosis in patients with locally advanced or metastatic esophagogastric cancer in a pooled analysis of three randomized, controlled trials.2 The prognostic index, which also included Eastern Cooperative Oncology Group performance status and serum alkaline phosphatase levels, has since been validated with the use of data from individual patients from this study.3

In a further exploratory analysis, when we limited our survival analysis to patients with metastatic disease, the median survival among patients treated with ECF was 9.0 months (95% CI, 7.4 to 10.6) as compared with 10.0 months (95% CI, 8.5 to 11.4) among patients treated with EOC (hazard ratio for death in the EOC group vs. the ECF group, 0.81; 95% CI, 0.65 to 1.02; P<0.001) (Figure 1B).

Patients with locally advanced disease and those with metastatic disease were evenly distributed among the four treatment groups in our study. We demonstrate here that the improvement in median survival among the patients receiving EOC as compared with ECF reported in 2008 for the per-protocol population is maintained when the analysis is limited to patients with metastatic disease.

David Cunningham, M.D.
Alicia F.C. Okines, M.B.,Ch.B., M.B.,Ch.B.
Sue Ashley, Ph.D.
Royal Marsden Hospital National Health Service Foundation Trust, Surrey, United Kingdom
david.cunningham@rmh.nhs.uk

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

3 References

1. 1

   Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008;358:36-46
   Full Text | Web of Science | Medline

2. 2

   Chau I, Norman AR, Cunningham D, Waters JS, Oates J, Ross PJ. Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer -- pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol 2004;22:2395-2403
   CrossRef | Web of Science | Medline

3. 3

   Chau I, Ashley S, Cunningham D. Validation of the Royal Marsden Hospital prognostic index in advanced esophagogastric cancer using individual patient data from the REAL 2 study. J Clin Oncol 2009;27:e3-e4
   CrossRef | Web of Science | Medline

Citing Articles (6)

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   Gun Min Kim, Hei-Cheul Jeung, Sun Young Rha, Hyo Song Kim, Inkyung Jung, Byung Ho Nam, Kyung Hee Lee, Hyun Cheol Chung. (2012) A randomized phase II trial of S-1-oxaliplatin versus capecitabine–oxaliplatin in advanced gastric cancer. European Journal of Cancer
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   Paulo M. Hoff, Everardo D. Saad, Frederico Costa, Anelisa K. Coutinho, Ricardo Caponero, Gabriel Prolla, Rene C. Gansl. (2011) Literature Review and Practical Aspects on the Management of Oxaliplatin-Associated Toxicity. Clinical Colorectal Cancer
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