American Society of Clinical Oncology Guideline on Weight-Based Dosing and Its Impact on Trial Design

Abstract

TO THE EDITOR: We fully support the new guidelines from the American Society of Clinical Oncology (ASCO) concerning chemotherapy dosing in obese patients. We have been concerned that underdosing occurs with dose capping for the obese (and for patients with a large surface area), which is widely practiced, and mandated in most clinical trial protocols. This results in a lack of toxicity data for fully dosed obese patients and potentially poorer patient outcomes. The lack of information about outcomes in trials for fully dosed patients with a large surface area has further persuaded clinicians to follow this practice routinely. Griggs et al note the lack of retrospective analyses of trial data to clarify the role of dose capping in the obese patients, although they do not cite our recent publication. In three recent United Kingdom Medical Research Center colorectal trials, dose capping was left to the discretion of individual clinicians. We conducted a retrospective study collating data from these trials to compare the outcomes of those patients with dose capping and those fully dosed. Of the 4,856 patients, 2,202 (45%) were classified as normal weight (body mass index [BMI] 25), 1,774 (37%) as overweight (BMI 25-29), and 880 (18%) as obese (BMI 30). There was a significant association between increasing weight subgroup and the proportion with a reduced dose (normal weight, 6%; overweight, 17%; obese, 55%; P .001). There was no evidence that obese patients experienced more toxicity in those fully dosed (normal weight, 21%; overweight, 20%; obese, 17%) or that reducing the doses of obese patients resulted in less toxicity (full dose, 17%; reduced dose, 16%). An important additional piece of information from our analysis was a suggestion that those obese patients who were given reduced doses had a slightly worse survival than those who were fully dosed (hazard ratio, 1.16; 95% CI, 1.00 to 1.35; P .055). Although not randomized, this adds considerable weight to the argument against dose capping. Thus our results complement and add to the evidence for the new ASCO guidelines. We would encourage clinical practice and future trial designs to adopt the new guidelines to ensure that obese and overweight patients are dosed appropriately.