title: Age and sex are independent predictors of 5-fluorouracil toxicity. Analysis of a large scale phase III trial.
abstract: BACKGROUND
  Cancer is most common in older age groups, but little information is available with regard to the impact of age on chemotherapy toxicity. This study was undertaken to determine if age is an independent risk factor for 5-fluorouracil (5-FU) toxicity.
  
  
  METHODS
  Toxicity data from a prospective, randomized, multiinstitution trial of 5-FU-based treatment for advanced colorectal cancer were analyzed. Toxicity for each organ system was graded. Individual organ toxicity proportions were compared using chi-square analysis. A logistic regression was performed using age (younger than 70 years vs. 70 years or older), sex, treatment arm, performance status, and length of therapy as model parameters to predict severe toxicity. Toxicity in 331 patients was analyzed.
  
  
  RESULTS
  Advanced age was significantly associated with the occurrence of any severe toxicity (58 vs. 36%, P < 0.001), leukopenia (24 vs. 10%, P < 0.005), diarrhea (24 vs. 14%, P = 0.01), vomiting (15 vs. 5%, P = 0.01), severe toxicity in more than 2 organ systems (10 vs. 3%, P = 0.02), and treatment mortality (9 vs. 2%, P = 0.01). By univariate analysis, age (P < 0.001) and sex (P < 0.0001) were independent predictors of severe toxicity. Twenty-two of 27 women age 70 years or older had severe toxicity.
  
  
  CONCLUSIONS
  Age 70 years or older and sex are risk factors for severe toxicity from 5-FU-based chemotherapy. Advanced age does not contraindicate the use of this type of chemotherapy, but close monitoring for multiple organ toxicities and vigorous supportive care of those with toxicity are required. Dosing decisions in older patients are difficult and must integrate assessments of organ function, comorbidities, overall physical status, and goals of treatment, in an effort to ensure the best possible outcome for these patients.
authors: Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263.
authors: B N
authors: BN
authors: Stein
authors: N J
authors: NJ
authors: Petrelli
authors: H O
authors: HO
authors: Douglass
authors: D L
authors: DL
authors: Driscoll
authors: G
authors: G
authors: Arcangeli
authors: N J
authors: NJ
authors: Meropol
mesh_terms: D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors; D014839:Vomiting / Q000139:chemically induced
chemical_list: D002955:Leucovorin; D005472:Fluorouracil