Impact of Physical Frailty on Early Intolerance to <scp>CAPOX</scp> Chemotherapy in Patients With Colon, Rectal, and Gastric Cancer

BACKGROUND: Patients with gastrointestinal cancer often present reduction in functional capacity and develop frailty, which increases the risk of chemotherapy intolerance. We investigated whether physical frailty is associated with early intolerance to CAPOX (capecitabine+oxaliplatin) in patients with colon, rectal, or gastric cancer. METHODS: This single-center observational study included patients from the Oncogeriatrics Outpatient Clinic at Clinical Hospital at UNICAMP between October 2021 and July 2024. Data included physical, clinical, and anthropometric measures. Frailty was assessed using the Fried criteria, along with planned and modified chemotherapy regimens. Early chemotherapy intolerance was defined as dose reduction, cycle delay, regimen change, or treatment discontinuation due to toxicity within the first three CAPOX cycles. Patients were classified as with or without early chemotherapy-related intolerance. RESULTS: Of 82 patients, 47 (57%) showed early intolerance to treatment. These patients were older, more frequently female, and smokers; no significant differences were observed in anthropometric and oncological variables, or in frailty criteria classification. The number of frailty criteria was associated with increased risk of intolerance (OR = 2.07; CI: 1.14-3.75; p = 0.01). Among individual components, self-reported exhaustion and reduced gait speed independently predicted higher risk (OR = 6.04; CI: 1.62-22.55; p = 0.007), while higher gait speed was protective (OR = 0.05; CI: 0.005-0.61; p = 0.01). CONCLUSION: Categorical physical frailty status was not associated with early toxicity in our cohort. However, the accumulation of physical frailty criteria showed a significant association with early toxicity. Among these criteria, gait speed emerged as one of the most relevant predictors of early toxicity in patients with colon, rectal, or gastric cancer treated with CAPOX. Objective assessment of the physical domain should be prioritized over subjective measures to improve treatment decisions and minimize adverse effects. Further research is needed to define standardized protocols for evaluating physical frailty in cancer patients.