Background: The activity of various chemotherapy regimens used in the treatment of advanced colorectal cancer is assessed by different groups of investigators and in various trials by what appear to be common criteria. However, there may be substantial inter-trial variation in the interpretation and application of these criteria which contributes to differences in response rates reported for the same regimen.
Materials and methods: This paper reviews the most prominent studies in this field and examines the factors which may influence the assessment of activity in clinical trials such as patient selection, the definition and application of response criteria, the methods of assessment of time to progression and duration of response, factors related to the therapeutic regimen and statistical methods. Each factor is critically discussed.
Results: The analysis confirms that there is a large variability among the different studies and that an inter-trial comparison is often impossible, with subsequent difficulties for clinicians in determining the true impact of therapies.
Discussion: After briefly commenting on the various issues, this review makes recommendations about how to achieve consistency among trials, for instance by using standard criteria, by extending the use of randomization even in phase II trials and by evaluating high quality, well conducted clinical trials in a meta-analysis, thereby making possible comparison across trials. The conclusions, although specific to colorectal cancer, are also applicable to other advanced malignancies.