Comparing irinotecan with best supportive care and infusional 5-fluorouracil: a critical evaluation of the results of two randomized phase III trials

Abstract

Two randomized phase III trials have been conducted in colorectal cancer patients with nonbulky metastatic disease who have failed first-line therapy with 5-fluorouracil (5-FU). In one trial, the use of 350 mg/m2 irinotecan was shown to significantly prolong survival relative to best supportive care. Patients receiving irinotecan also experienced higher quality of life than the controls. In the second trial, the same regimen of irinotecan resulted in a significantly longer median survival than the comparator regimen consisting of best estimated infusional 5-FU. Quality of life was similar across treatments. These two trials were large, well-conducted, and used appropriate methodology for patient selection, measurement of outcome, and statistical analysis. The results of these trials have implications for everyday clinical practice. When appropriate, irinotecan should be offered to patients who have failed 5-FU. Irinotecan should be the reference arm for future studies of investigational second-line drugs; the potential of irinotecan (alone or in combination) in the first-line and adjuvant treatment of colorectal cancer now needs to be evaluated.