Standard Chemotherapy for Gastric Carcinoma: Is It a Myth?

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.2001.19.10.2765 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11352971 Standard Chemotherapy for Gastric Carcinoma: Is It a Myth? N. C. TebbuttxN. C. TebbuttSearch for articles by this author , A. NormanxA. NormanSearch for articles by this author , M. HillxM. HillSearch for articles by this author , D. CunninghamxD. CunninghamSearch for articles by this author Jaffer A. AjanixJaffer A. AjaniSearch for articles by this author Show More Royal Marsden Hospital, Sutton United KingdomThe University of Texas M.D. Anderson Cancer Center, Houston, TX https://doi.org/10.1200/JCO.2001.19.10.2765 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15052001In Reply:I find the letter by Tebbutt et al addresses many doubts I had raised in my previous correspondence regarding standard chemotherapy for advanced gastric carcinoma.1 The low level of acceptance of the epirubicin, cisplatin, and fluorouracil (ECF) regimen as the standard therapy in this country is not because epirubicin has been, until recently, an investigational agent. The oncologists could have easily substituted it with doxorubicin. However, the anthracycline era for gastric cancer has slowly ended in the United States with the demise of doxorubicin-containing regimens (such as fluorouracil, doxorubicin, and mitomycin [FAM]; fluorouracil, doxorubicin, and methyl-lomostine [FAME]; etoposide, doxorubicin, and cisplatin [EAP]; or fluorouracil, doxorubicin, and methotrexate [FAMTX]; and so on), and it may not be resurrected because of a significant influx of new agents now available for investigation or for off-label use.I wish to emphasize that the median survival duration as a result of a winning regimen must be substantially longer than 9 months (that seems to be the norm so far for nearly all combinations including ECF) in a well-designed and executed trial. That would establish a new standard. It does not have to be precisely ≥ 12 months. In that light, the 11.6-month median survival duration from ECF in a trial comparing ECF and mitomycin, epirubicin, and fluorouracil is intriguing. A publication describing these data in detail would be of interest. I would, however, de-emphasize the 11-month median survival duration from ECF in patients treated at the Royal Marsden Hospital in the trial reported by Webb et al,2 because this constitutes a subgroup analysis and, therefore, is subject to criticism.What can one say about the patients entered onto an advanced disease trial but then rendered free of disease after a surgical resection? This group of patients is certainly likely to fare better than the patients who are not rendered disease-free. Thus the issue of dissimilar number of patients rendered disease-free (for whatever duration) in two treatment arms of the phase III trial reported by Webb et al2 is still unsettling. There was no stratification of any sort described in their report, but by the stroke of luck, only four more patients with only locally advanced disease were randomized to FAMTX than to ECF.1 One also wonders about more precise clinical stage of cancer of these patients. Tebbutt et al argue that more patients were rendered disease-free because ECF was more active (or effective). This notion echos one of the principles concretized in the preoperative strategy for gastric carcinoma with the objective of improving the curative resection rate and survival. However, the strength of this strategy is diluted in the trial that enrolled a majority of patients who had widely metastatic cancer. If a disproportionate number of patients are rendered disease free (after surgery) in an advanced-disease phase III trial, the conclusions would be misleading. This is one reason to argue from an opposite perspective. What is the influence of rendering more patients surgically free of disease in the ECF arm versus the FAMTX arm? The answer to this question is unknowable.In the currently ongoing, multinational, Aventis-sponsored, phase III trial (v-325) for patients with advance gastric carcinoma, patients with only locally advanced disease, who could be potentially rendered disease-free by surgery, are not eligible for enrollment. This clause was intentionally inserted to avoid skewing the results.I applaud the passionate dedication of the investigators from Royal Marsden Hospital to gastric cancer research. Not only they have developed new regimens but followed up with phase III trials to put their ideas in a proper perspective.1. Ajani JA: Standard chemotherapy for gastric carcinoma: Is it a myth? J Clin Oncol 18:: 4001,2000-4003, Link, Google Scholar2. Webb A, Cunningham D, Scarffe JH, et al: Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and the methotrexate in advanced esophagostric cancer. J Clin Oncol 15:: 261,1997-267, Link, Google Scholar