TOXICITY OF FLUOROURACIL IN PATIENTS WITH ADVANCED COLORECTAL-CANCER - EFFECT OF ADMINISTRATION SCHEDULE AND PROGNOSTIC FACTORS

Purpose: Fluorouracil (5-FU) continuous infusion is superior to 5-FU b olus in patients with advanced colorectal cancer, but the survival dif ference between the two treatments is small and, therefore, the differ ence in toxicity profile is crucial in choosing a treatment for indivi dual patients. Materials and Methods: We conducted a metaanalysis of a ll randomized trials that compared 5-FU bolus with 5-FU CI, based on i ndividual data from 1,219 patients, to compare the toxicity of the two schedules of 5-FU administration and to identify predictive factors f ar toxicity. The toxicities considered were World Health Organization (WHO) grade 3 to 4 anemia, thrombopenia, leukopenia, neutropenia, naus ea/vomiting, diarrhea, mucositis, and hand-foot syndrome. Results: Hem atologic toxicity, mainly neutropenia, was mare frequent with 5-FU bol us than with 5-FU CI (31% and 4% respectively; P < .0001). Hand-foot s yndrome was less frequent with 5-FU bolus than with 5-FU CI (13% and 3 4%, respectively; P < .0001). There was no difference between the two treatment groups in terms of other nonhematalogic toxicities. Independ ent prognostic factors were age, sex, and performance status for nonhe matologic toxicities, performance status, and treatment for hematologi c toxicities, and age, sex, and treatment for hand-foot syndrome. Conc lusion: Based on a large data set this study confirmed and quantified the toxicity profile of the two schedules of administration of 5-FU an d allowed the identification of clinical predictors of toxicity. (C) 1 998 by American Society of Clinical Oncology.