Correspondence

Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer

N Engl J Med 2008; 358:1965May 1, 2008

Article

To the Editor:

Cunningham et al. (Jan. 3 issue)1 state that capecitabine and oxaliplatin are equivalent to fluorouracil and cisplatin in esophagogastric cancer. One disadvantage of their study is that patients with squamous-cell carcinoma were not excluded. Furthermore, it seems that combinations of capecitabine and oxaliplatin are not less toxic or more effective but their cost is 5 to 10 times that of therapy with epirubicin, cisplatin, and fluorouracil (ECF). Moreover, peripheral neuropathy occurs more frequently with oxaliplatin.2,3 We therefore see no better profile for capecitabine and oxaliplatin in patients with advanced esophagogastric cancer.

Edwin Bölke, M.D.
Matthias Peiper, M.D.
Wilfried Budach, M.D.
University of Düsseldorf, D-40225 Düsseldorf, Germany
boelke@med.uni-duesseldorf.de

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

   Mauer AM, Kraut EH, Krauss SA, et al. Phase II trial of oxaliplatin, leucovorin and fluorouracil in patients with advanced carcinoma of the esophagus. Ann Oncol 2005;16:1320-1325
   CrossRef | Web of Science | Medline

3. 3

   Kannarkat G, Lasher EE, Schiff D. Neurologic complications of chemotherapy agents. Curr Opin Neurol 2007;20:719-725
   Web of Science | Medline

Author/Editor Response

In our study, the oral prodrug capecitabine was as effective as fluorouracil, with a trend toward superiority and with similar toxicity. Patients with cancer often prefer oral alternatives to intravenous treatments, provided that efficacy is maintained.1 The convenience for patients is a key consideration. During ECF therapy, fluorouracil is administered continuously throughout treatment (up to 6 months) through a central venous access device and an ambulatory pump requiring either community or hospital-based support. Such therapy is associated with morbidity, (i.e., infection, pain, thrombosis, and hospitalization).

As compared with cisplatin, oxaliplatin was associated with less thromboembolism, renal toxicity, alopecia, and neutropenia and required no additional hydration (considerably shortening the duration of outpatient visits). Oxaliplatin is widely used in colorectal cancer, in which peripheral neuropathy is managed by dose adjustment. Among patients who received epirubicin, oxaliplatin, and capecitabine (EOX), the median overall survival (11.2 months) was the longest period observed in our trials evaluating ECF in esophagogastric cancer, in which patients with advanced squamous-cell cancer accounted for less than 10% of 1002 patients.2,3

Incremental treatment-related costs will probably be less than those suggested by Bölke et al., since oxaliplatin is available as a generic drug in Europe. Drug costs may be offset by ECF-related nondrug costs, inconvenience to patients, and toxicity.

David Cunningham, M.D.
Naureen Starling, M.R.C.P.
Royal Marsden Hospital National Health Service Foundation Trust, London SW3 6JJ, United Kingdom

3 References

1. 1

   Liu G, Franssen E, Fitch MI, Warner E. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 1997;15:110-115
   Web of Science | Medline

2. 2

   Webb A, Cunningham D, Scarffe JH, et al. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 1997;15:261-267
   Web of Science | Medline

3. 3

   Ross P, Nicolson M, Cunningham D, et al. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) with epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 2002;20:1996-2004
   CrossRef | Web of Science | Medline