Epirubicin, Cisplatin, and Protracted Venous-Infusion Fluorouracil in Advanced Esophagogastric Cancer
Authors: Gregory D. Leonard, Sen H. Zhuang, Jean L. Grem, Paul J. Ross, David Cunningham
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.99.125 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12351613 Epirubicin, Cisplatin, and Protracted Venous-Infusion Fluorouracil in Advanced Esophagogastric Cancer Gregory D. LeonardxGregory D. LeonardSearch for articles by this author , Sen H. ZhuangxSen H. ZhuangSearch for articles by this author , Jean L. GremxJean L. GremSearch for articles by this author Paul J. RossxPaul J. RossSearch for articles by this author , David CunninghamxDavid CunninghamSearch for articles by this author Show More National Cancer Institute, Bethesda, MDRoyal Marsden Hospital, London and Sutton, United Kingdom https://doi.org/10.1200/JCO.2002.99.125 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01102002In Reply:Drs Leonard, Zhuang, and Grem suggest patients with locally advanced squamous esophageal cancer should be treated with concurrent chemoradiation using cisplatin and fluorouracil (5-FU)-based therapy. We agree that this is the optimal strategy for patients in whom radical radiation can be delivered. In the study we reported,1 40 patients with squamous esophageal cancer were included in a total of 580 patients randomized between epirubicin, cisplatin, and protracted venous-infusion 5-FU (ECF) and mitomycin, cisplatin, and protracted venous-infusion 5-FU for the treatment of advanced esophagogastric cancer. Twenty-one patients with squamous esophageal cancer had metastatic disease, and 18 had locally advanced disease not suitable for radical radiotherapy. Thus no patient entered onto the largest randomized trial evaluating chemotherapy in esophagogastric cancer was suitable for concurrent chemoradiation treatment.Leonard et al also suggest that the role of chemotherapy in patients with squamous esophageal cancer is not well established on the basis of two studies. Levard et al2 reported that the combination of cisplatin and a 5-day infusion of 5-FU did not improve survival compared with a control group. However, this study included 62 patients randomized after complete resection. A subgroup analysis for survival was conducted on the 94 patients randomized in the palliative setting, but the study was not powered to detect a survival difference in this small number of patients. A randomized phase II study demonstrated both a higher response rate (35% v 19%) and a 5-week improvement in median survival (33 weeks v 28 weeks) with cisplatin and 5-FU compared with cisplatin alone.3 The survival difference was not significant, but the study was not powered to detect an improvement in survival. Consequently, neither of these studies was adequately powered to conclude that there is no survival advantage from chemotherapy in patients with squamous esophageal cancer who are not candidates for concurrent chemoradiation. ECF has previously demonstrated a median survival of 8.4 months in squamous esophageal cancer.4 This survival time is similar to the survival observed for ECF in the two reported randomized studies, 8.7 and 9.4 months.1,5 In addition, ECF has demonstrated an objective radiologic response rate of 43% and endoscopic response rate of 48% in squamous esophageal cancer.4 This response rate is similar to that observed with ECF in both randomized trials.1,5 Furthermore, the response rates for patients with esophageal cancers in the current study were not significantly different from those achieved in gastric cancer.1 These observations indicate that ECF has similar efficacy in squamous esophageal cancer as it does in gastric adenocarcinoma. On this basis, we believe that ECF may be considered a reference treatment for patients with squamous esophageal cancer who are not candidates for radical radiotherapy as part of chemoradiation with curative intent.1. 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 20:: 1994,2002-2004, Google Scholar2. Levard H, Pouliquen X, Hay J-M, et al: 5-Fluorouracil and cisplatin as palliative treatment of advanced oesophageal squamous cell carcinoma: A multicentre randomised controlled trial. Eur. J Surg 164:: 849,1998-857, Google Scholar3. Bleiberg H, Conroy T, Paillot B, et al: Randomised phase II study of cisplatin and 5-fluorouracil (5-FU) versus cisplatin alone in advanced squamous cell oesophageal cancer. Eur J Cancer 33:: 1216,1997-1220, Crossref, Medline, Google Scholar4. Andreyev H, Norman A, Cunningham D, et al: Squamous oesophageal cancer can be downstaged using protracted venous infusion of 5-fluorouracil with epirubicin and cisplatin (ECF). Eur J Cancer 31A:: 2209,1995-2214, Medline, Google Scholar5. 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 15:: 261,1997-267, Link, Google Scholar