title: Double-blind randomised placebo-controlled phase III study of an E. coli extract plus 5-fluorouracil versus 5-fluorouracil in patients with advanced colorectal cancer.
abstract: The primary aim of this study was to evaluate the toxicity (mucositis, diarrhea and leucopenia) of a therapy with 5-fluorouracil (CAS 51-21-8; 5-FU) plus an E. coli extract (LC-Extract, Laves coli extract, Colibiogen inject, cell-free soluble fraction from lysed E. coli, Laves strain) in comparison with 5-FU plus placebo. Secondary endpoints included general toxicity, response rate according to WHO, survival time and quality of life. 164 patients with advanced colorectal cancer were enrolled in this randomised, placebo-controlled, double-blind, multicenter phase III study. The treatment consisted of 0.167 ml/kg/d LC-Extract or placebo followed by 500-750 mg/m2/d 5-FU on five consecutive days, repeated every three weeks for up to six treatment cycles. 158 (77 verum, 81 placebo) patients were evaluable for toxicity, 144 (72 verum, 72 placebo) evaluable for response. The therapy with LC-Extract was well tolerated. Adverse events that occurred during the study were mainly judged as 5-FU- or tumor-related. Toxicity from treatment with 600 mg/m2/d 5-FU in both treatment groups was very low. After treatment with 750 mg/m2/d 5-FU patients in the placebo-group experienced a higher CTC toxicity than in the LC-Extract groups. Remission rate and survival time showed a slight trend in favour of LC-Extract. These results suggest a positive benefit-risk ratio of the additional application of LC-Extract to 5-FU in the treatment of advanced colorectal cancer especially for administration of high doses of 5-FU.
authors.affiliation: Department Medical Oncology, Tumor Biology Centre, Albert-Ludwigs-University, Freiburg i. Br., Germany. unger@tumorbio.uni-freiburg.de
authors.forename: C
authors.initials: C
authors.lastname: Unger
authors.forename: B
authors.initials: B
authors.lastname: Häring
authors.forename: A
authors.initials: A
authors.lastname: Kruse
authors.forename: A
authors.initials: A
authors.lastname: Thumann
authors.forename: B
authors.initials: B
authors.lastname: Schneider
authors.forename: C
authors.initials: C
authors.lastname: Clemm
authors.forename: B
authors.initials: B
authors.lastname: Weber
authors.forename: H D
authors.initials: HD
authors.lastname: Clevert
authors.forename: S
authors.initials: S
authors.lastname: Hockertz
authors.forename: M B
authors.initials: MB
authors.lastname: Kalousek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D004926:Escherichia coli / Q000737:chemistry*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil