P Piedbois1, M Buyse. 1. Department of Oncology, Hôpital Henri Mondor, Créteil, France.
Abstract
BACKGROUND AND DESIGN: We previously reported a meta-analysis of all randomized clinical trials comparing 5-FU to 5-FU plus intravenous d.l. leucovorin (LV) in patients with advanced colorectal cancer. RESULTS: The meta-analysis confirmed the advantage of 5-FU/LV over 5-FU alone in terms of response rate: overall, the response rate was 11% with 5-FU alone vs 23% with 5-FU/LV (p < 10(-7)). At the same time, it was showed that tumor regression can not be considered a surrogate end point for survival in patients with advanced colorectal cancer: no significant survival advantage was observed for patients allocated to 5-FU/LV. The present paper focuses on the interest of meta-analysis to study the role of the biomodulation of 5-FU by LV. This approach is compared with the analysis of individual clinical trials in terms of power, bias and credibility. It is argued that for the meta-analysis to be reliable, individual patient data from all available studies must be used, rather than summary data extracted from published papers. CONCLUSION: It is concluded that meta-analysis is very useful as a tool to explore and summarize available data on a given clinical problem, though its purpose is not to recommend any treatment modality. This meta-analysis has confirmed both the benefit of biomodulation of 5-FU by LV, and the limitations of the current modalities to impact significantly on overall patient survival. Further laboratory and clinical research is warranted on the biomodulation of 5-FU by LV.
BACKGROUND AND DESIGN: We previously reported a meta-analysis of all randomized clinical trials comparing 5-FU to 5-FU plus intravenous d.l. leucovorin (LV) in patients with advanced colorectal cancer. RESULTS: The meta-analysis confirmed the advantage of 5-FU/LV over 5-FU alone in terms of response rate: overall, the response rate was 11% with 5-FU alone vs 23% with 5-FU/LV (p < 10(-7)). At the same time, it was showed that tumor regression can not be considered a surrogate end point for survival in patients with advanced colorectal cancer: no significant survival advantage was observed for patients allocated to 5-FU/LV. The present paper focuses on the interest of meta-analysis to study the role of the biomodulation of 5-FU by LV. This approach is compared with the analysis of individual clinical trials in terms of power, bias and credibility. It is argued that for the meta-analysis to be reliable, individual patient data from all available studies must be used, rather than summary data extracted from published papers. CONCLUSION: It is concluded that meta-analysis is very useful as a tool to explore and summarize available data on a given clinical problem, though its purpose is not to recommend any treatment modality. This meta-analysis has confirmed both the benefit of biomodulation of 5-FU by LV, and the limitations of the current modalities to impact significantly on overall patient survival. Further laboratory and clinical research is warranted on the biomodulation of 5-FU by LV.
Authors: Ferdinand Rombout; Leon Aarons; Mats Karlsson; Anthony Man; France Mentré; Peter Nygren; Amy Racine; Hans Schaefer; Jean-Louis Steimer; Iñaki Troconiz; Achiel van Peer Journal: J Pharmacokinet Pharmacodyn Date: 2004-12 Impact factor: 2.745