FACTORS INFLUENCING RESPONSE RATES FOR ADVANCED COLORECTAL-CANCER CHEMOTHERAPY

Background: The activity of various chemotherapy regimens used in the treatment of advanced colorectal cancer is assessed by different group s of investigators and in various trials by what appear to be common c riteria. However, there may be substantial inter-trial variation in th e interpretation and application of these criteria which contributes t o differences in response rates reported for the same regimen. Materia ls and methods: This paper reviews the most prominent studies in this field and examines the factors which may influence the assessment of a ctivity in clinical trials such as patient selection, the definition a nd application of response criteria, the methods of assessment of time to progression and duration of response, factors related to the thera peutic regimen and statistical methods. Each factor is critically disc ussed. Results: The analysis confirms that there is a large variabilit y among the different studies and that an inter-trial comparison is of ten impossible, with subsequent difficulties for clinicians in determi ning the true impact of therapies. Discussion: After briefly commentin g on the various issues, this review makes recommendations about how t o achieve consistency among trials, for instance by using standard cri teria, by extending the use of randomization even in phase II trials a nd by evaluating high quality, well conducted clinical trials in a met a-analysis, thereby making possible comparison across trials. The conc lusions, although specific to colorectal cancer, are also applicable t o other advanced malignancies.