WHAT CAN WE LEARN FROM A METAANALYSIS OF TRIALS TESTING THE MODULATION OF 5-FU BY LEUCOVORIN

Background and design: We previously reported a meta-analysis of all r andomized 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-F U alone vs 23% with 5-FU/LV (p < 10(-7)). At the same time, it was sho wed that tumor regression can not be considered a surrogate end point for survival in patients with advanced colorectal cancer: no significa nt survival advantage was observed for patients allocated to 5-FU/LV. The present paper focuses on the interest of meta-analysis to study th e role of the biomodulation of 5-FU by LV. This approach is compared w ith the analysis of individual clinical trials in terms of power, bias and credibility. It is argued that for the meta-analysis to be reliab le, individual patient data from all available studies must be used, r ather than summary data extracted from published papers. Conclusion: I t is concluded that meta-analysis is very useful as a tool to explore and summarize available data on a given clinical problem, though its p urpose 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 over all patient survival. Further laboratory and clinical research is warr anted on the biomodulation of 5-FU by LV.