Elevated body mass index (BMI) is associated with reduced average relative dose intensity of adjuvant chemotherapy in colorectal cancer: the OCTOPUS trials consortium
Session type: E-poster/poster
Adjuvant chemotherapy (ACT) for colorectal cancer (CRC) is dosed according to body surface area (BSA). Dose capping is common for patients with a BSA ≥2.2m2, and may reduce relative dose intensity (RDI). A RDI <85% is associated with reduced cancer survival, hence, dose-capping-related RDI reductions might reduce survival in obesity. Big-data with deeply phenotyped dosing schedules may better elucidate these relationships.
We included individual-level participant data from two CRC-ACT randomised-trials (MOSAIC: 5-fluorouracil/leucovorin (5FU) (control arm); SCOT: 5FU/Oxaliplatin (mFOLFOX6) & capecitabine/oxaliplatin (CAPOX) regimens), with derivable BMI and ACT data. BSA was calculated with the Mosteller formula using actual body weight (ABW). Dose capping was defined as receipt of <95% of the standard ABW-derived 1st cycle dose. Average RDI (ARDI) was defined as a percentage of actual to expected dose intensity (DI; cumulative dose (mg/m2 of BSA) divided by treatment duration in weeks) averaged across drug regimens. ARDI was dichotomised as <85% or ≥85%. Statistical analysis consisted of ordinal tests for trend and multivariable logistic regression, to explore BMI-ARDI relationships by regimen.
A combined total of 6865 patients were eligible. Proportions of underweight, normal, overweight and obese BMI were 3.3%, 49.5%, 35.0% and 12.3% for MOSAIC; 1.3%, 36.0% 40.4% and 22.2%, for SCOT. Proportions of patients dose capped and receiving ARDI <85% are presented in Table 1.
Compared with normal BMI, obese was associated with increased odds of receiving <85% ARDI in MOSAIC-5FU (OR: 2.36; 95%CI: 1.46, 3.83; p <0.001) and SCOT-CAPOX (OR: 1.44; 95%CI: 1.20, 1.71; p <0.001), but not SCOT-FOLFOX.
Obesity was associated with increased odds of receiving <85% ARDI in MOSAIC-5FU and SCOT-CAPOX regimens, suggesting potentially sub-optimal dosing.
Sub-optimal chemotherapy dosing of obese patients might reduce CRC survival. Further work will explore BMI-ARDI-survival relationships.