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

The primary aim of this study was to evaluate the toxicity (mucositis, diar rhea and leucopenia) of a therapy with 5- fluorouracil (CAS 51-21-8; 5-FU) plus an E. coli extract (LC-Extract, raves coli extract, Colibiogen(R) inje ct, cell-free soluble fraction from lysed E. coli, raves strain) in compari son 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 randomis ed, placebo-controlled, double-blind, multicenter phase III study. The trea tment consisted of 0.167 ml/kg/d LC-Extract or placebo followed by 500-750 mg/m(2)/d 5-FU on fire consecutive days, repeated every three weeks for up to six treatment cycles. 158 (77 verum, 81 placebo) patients were evaluable for toxicity, 144 (72 ve rum, 72 placebo) evaluable for response. The therapy with LC-Extract was we ll tolerated. Adverse events that occurred during the study were mainly jud ged as 5-FU- or tumor-related. Toxicity from treatment with 600 mg/m(2)/d 5 -FU In both treatment groups was very low. After treatment with 750 mg/m(2) /d 5-FU patients in the placebo-group experienced a higher CTC toxicity tha n in the LC-Extract group. 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 appli cation of LC-Extract to 5-FU in the treatment of advanced colorectal cancer especially for administration of high doses of 5-FU.