|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 25, No 6 (February 20), 2007: pp. 729 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.09.4896
Chemotherapy for Advanced Gastric CancerDepartment of Hematology and Oncology, Krankenhaus Nordwest, Frankfurt, Germany
Trium Analysis Online GmbH, Munich, Germany To the Editor: Dr Wagner et al1 recently published an article presenting a meta-analysis of randomized trials on first-line chemotherapy in patients with advanced gastric cancer. The authors analyzed randomized studies using chemotherapy versus best support care, combination versus single-agent chemotherapy, and fluorouracil (FU), cisplatin, and anthracycline versus FU and cisplatin chemotherapy combinations. The results of the analysis included a significant survival benefit for patients receiving a FU and cisplatin-containing regimen with anthracycline versus those receiving FU and cisplatin combinations without anthracycline. The mean benefit for survival was approximately 2 months. The authors concluded that their findings support the results of previous trials, proposing the epirubicin, cisplatin, and FU (ECF) regimen as standard treatment for patients with advanced gastric cancer. The authors further stated that the survival advantage for docetaxel combined with cisplatin and FU (DCF) as compared with cisplatin and FU (CF) alone in a recent phase III trial was minor, though statistically significant (median survival, 9.2 v 8.6 months, respectively; P = .02), and they doubted about whether DCF represents a true therapeutic advance over the established regimen. We propose exercising caution in interpreting the results of the comparison of FU, cisplatin, and anthracycline to FU and cisplatin combinations in this meta-analysis, and we do not share the author's interpretation of the data for DCF. The comparison of FU and cisplatin versus FU, cisplatin, and anthracycline combinations in the meta-analysis was based on 501 patients from three randomized trials. Three hundred thirty-four (67%) of these 501 patients were obtained from a study published by Ross et al2 in 2002. This study originally compared protracted, continuous infusion of FU in combination with cisplatin and epirubicin (ECF) with protracted continuous infusion of escalated-dose FU combined with cisplatin and mitomycin (MCF) in 580 patients with locally advanced or metastatic gastric or esophageal cancer. The primary end point of the study was overall survival, assuming superiority of MCF to ECF. The trial, however, demonstrated the equivalence of both regimens in terms of response rate, progression-free survival, and overall survival. MCF was associated with increased toxicity and worse global quality of life scores at 3 and 6 months, which was probably related to the higher dose of FU in the MCF arm. Wagner et al3 selected a distinct subpopulation (patients with gastric and gastroesophageal junction adenocarcinoma) of the Ross study for the meta-analysis. Notably, this subgroup has never been published, nor was it specifically indicated or discussed in the original publication by Ross et al.2 The selection of data to be analyzed in meta-analyses is critical, especially when few studies are included, and subgroup analyses are generally susceptible for selection bias. The study published by Ross et at2 included 373 patients with gastric or gastroesophageal junction adenocarcinoma, and there were significantly more patients with locally advanced disease in the ECF arm (P = .03). No detailed information was provided by Wagner et al3 on what basis 334 out of a total of 580 patients in the Ross trial were selected for the meta-analysis and whether important prognostic factors were balanced in this subgroup. In addition, significant issues were not appropriately discussed, which include but are not limited to the question of whether the possibility of an adverse effect of the increased toxicity of MCF could have affected the results in the subgroup analyzed. The TAX325 study (predefined end points; 95% power; two-sided log-rank test; homogenous patient population with 96% having metastatic disease) has shown that DCF is clearly superior to CF in terms of quality of life, response rate, time to progression, and overall survival.4 In our view, Wagner et al1 underestimate the improvement in survival achieved by DCF. DCF was associated with a 27% relative improvement in overall survival at 1 year and doubled the overall survival rate at 2 years as compared with CF alone (2-year survival rate, 18.8 v 8.9%, respectively). These differences are reflected by a positive log-rank test, which is a robust test that evaluates the hazard function for outcomes over time and accounts for follow-up interval and censorship appropriately. Evidence-based medicine must be based on all of the evidence including meta-analyses and reviews. One should, however, recognize that the highest level of evidence is found in the classical individual randomized phase III study of high-quality design and adequate power analyzed by predefined methods that make optimal use of all instruments for measuring the defined objectives possible. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Employment: N/A Leadership: N/A Consultant: Salah-Eddin Al-Batran, Sanofi-aventis Stock: N/A Honoraria: N/A Research Funds: N/A Testimony: N/A Other: N/A REFERENCES
1. Wagner AD, Grothe W, Haerting J, et al: Chemotherapy in advanced gastric cancer: A systematic review and meta-analysis based on aggregate data. J Clin Oncol 24:2903-2909, 2006 2. 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 20:1996-2004, 2002 3. Wagner AD, Grothe W, Behl S, et al: Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 18:CD004064, 2005 4. Ajani JA, Van Cutsem E, Moiseyenko V, et al: Docetaxel (D), cisplatin, 5-fluorouracil compare to cisplatin (C) and 5-fluorouracil (F) for chemotherapy-naive patients with metastatic or locally recurrent, unresectable gastric carcinoma (MGC): Interim results of a randomized phase III trial (V325). Proc Am Soc Clin Oncol 22:249, 2003 (abstr 99)
Related Reply
Related Article
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
