title: Impact of 5-fluorouracil rechallenge on subsequent response and survival in advanced colorectal cancer: pooled analysis from three consecutive randomized controlled trials.
abstract: 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.
authors.affiliation: Department of Medicine, Royal Marsden Hospital, London and Surrey, UK.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yeoh
authors.forename: Ian
authors.initials: I
authors.lastname: Chau
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: Andy R
authors.initials: AR
authors.lastname: Norman
authors.forename: Mark
authors.initials: M
authors.lastname: Hill
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D016685:Mitomycin; D005472:Fluorouracil