title: Chemotherapy dose reductions in obese patients with colorectal cancer.
abstract: BACKGROUND
  In cancer patients with a large Body Surface Area, chemotherapy drug doses are often reduced, as studies have suggested that their pharmacokinetics may be altered. However, this strategy may result in underdosing obese patients.
  
  
  METHODS
  In three Medical Research Council trials of chemotherapy for advanced colorectal cancer, dose reductions were not mandated. This provided the opportunity to compare the toxicity levels in those obese patients fully dosed and to investigate if those under dosed experienced a worse survival. Body Mass Index (BMI) was used to classify patients as normal weight (BMI < 25), overweight (BMI 25-29), or obese (BMI 30+).
  
  
  RESULTS
  Of the 4781 patients, 2158 (45%) were classified as normal weight, 1753 (37%) as overweight, and 870 (18%) as obese. There was no evidence that, in those patients fully dosed, obese patients experienced more toxicity or that dose-reducing obese patients resulted in less toxicity. However, there was a suggestion that those obese patients who were given reduced doses had a worse progression-free survival [hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.06-1.39, P = 0.006] and a slightly worse overall survival (HR 1.12, 95% CI 0.96-1.30, P = 0.152).
  
  
  CONCLUSIONS
  These results, although not a randomised comparison, do not support the policy of reducing chemotherapy doses for obese patients with colorectal cancer.
authors.affiliation: Pharmacy, University College London Hospital, London.
authors.forename: P
authors.initials: P
authors.lastname: Chambers
authors.affiliation: Pharmacy, University College London Hospital, London.
authors.forename: S H
authors.initials: SH
authors.lastname: Daniels
authors.affiliation: Medical Research Council Clinical Trials Unit, London, UK. Electronic address: lt@ctu.mrc.ac.uk.
authors.forename: L C
authors.initials: LC
authors.lastname: Thompson
authors.affiliation: Medical Research Council Clinical Trials Unit, London, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Stephens
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015992:Body Mass Index; D001830:Body Surface Area; D015179:Colorectal Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D006801:Humans; D009765:Obesity / Q000150:complications*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents