Medline ® Abstract for Reference 4
of 'Systemic chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations'
Impact of 5-fluorouracil rechallenge on subsequent response and survival in advanced colorectal cancer: pooled analysis from three consecutive randomized controlled trials.
Yeoh C, Chau I, Cunningham D, Norman AR, Hill M, Ross PJ
Clin Colorectal Cancer. 2003;3(2):102.
The aim of this analysis is to evaluate the effect of 5-fluorouracil (5-FU) rechallenge on subsequent response and survival in patients with advanced colorectal cancer (CRC). Between April 1992 and August 1998, 613 patients were enrolled into 3 consecutive prospective randomized controlled trials assessing first-line infused 5-FU in patients with advanced CRC. All patients had a planned maximum treatment period of 6 months. Those with responding or stable disease at the end of 6 months were observed off treatment. On subsequent disease progression, patients were retreated with 5-FU alone (5-FU group) or 5-FU plus mitomycin C (MMC group). Ninety-three patients have been retreated (5-FU group, n = 71; MMC group, n = 22). The median age was 60 years (range, 38-79 years), and the median time to rechallenge was 11.7 months (5-FU group, 11.7 months; MMC group, 11.4 months). Seventeen percent of patients had an objective response to rechallenge (5-FU group, 13%; MMC group, 27%). The median survival was 14.8 months (5-FU group, 15.2 months; MMC group, 10.5 months; log-rank test, P = 0.23) and the median failure-free survival was 5.4 months (5-FU group, 5.6 months; MMC group, 3.7 months; log-rank test, P = 0.06). On multivariate analysis, a prolonged treatment-free interval of>12 months (hazard ratio [HR], 0.57; 95% CI, 0.35-0.94; P =0.027) and good performance status of 0/1 (HR, 0.38; 95% CI, 0.22-0.68; P = 0.001) were associated with better overall survival. In conclusion, a proportion of patients who experienced a prolonged period of tumor control with first-line infused 5-FU therapy and had a planned treatment interruption, retained 5-FU sensitivity and had prolonged survival with 5-FU rechallenge.
Department of Medicine, Royal Marsden Hospital, London and Surrey, UK.