Chemotherapy dose reductions in obese patients with colorectal cancer

Abstract

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. 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+). 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). These results, although not a randomised comparison, do not support the policy of reducing chemotherapy doses for obese patients with colorectal cancer.