Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study

Background: Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy. Methods: Survival outcomes and toxicity data of obese (body mass index [BMI] >= 30 kg/m(2)), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.e. fully weight-based dosed - versus dose-reduced group). Multivariate analyses on relapse free survival (RFS) and overall survival (OS) were conducted to adjust for baseline prognostic factors using Cox regression model. Results: 13.4% (280 of 2094 patients) had a BMI >= 30 kg/m(2), and 5.3% had both a BMI >= 30 kg/m(2) and a body surface area (BSA) >= 2 m(2). Dose reductions occurred in 16.1% of patients with a BMI >= 30 kg/m(2) and 32.4% with BMI >= 30 kg/m(2) and BSA >= 2 m(2), respectively. In patients with BMI >= 30 kg/m(2), multivariate analysis demonstrated a trend towards better RFS in the fully dosed compared to the dose-reduced group (Hazard ratio (HR): 0.69, 95% CI: 0.43-1.09; p = 0.11); however, there was no statistically significant difference in OS. In patients with BMI > 30 kg/m(2) and BSA > 2 m(2), multivariate analysis demonstrated better RFS in fully dosed compared with dose-reduced patients (HR: 0.48, 95% CI: 0.27-0.85; p = 0.01) and a strong trend towards better OS (HR: 0.53, 95% CI: 0.28-1.01; p = 0.052). This group comprised predominantly of men. Conclusions: Data support the recommendation of using fully dosed chemotherapy for the adjuvant treatment in obese patients with colon cancer. (C) 2018 Elsevier Ltd. All rights reserved.