Incidence and Risk Factors of Non-neutropenic Enterocolitis With Adjuvant Capecitabine and Oxaliplatin Chemotherapy in Colorectal Cancer

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BACKGROUND: Following the IDEA collaboration, the use of capecitabine and oxaliplatin (CAPOX regimen) for adjuvant colorectal cancer treatment has increased. While CAPOX is associated with higher rates of diarrhea, non-neutropenic enterocolitis (NNE) and related hospitalizations have not been well described. PATIENTS AND METHODS: We performed a retrospective cohort study of patients treated with adjuvant CAPOX, mFOLFOX6 (infusional 5-fluorouracil, leucovorin, and oxaliplatin), and capecitabine between 2015 and 2023 at 2 hospitals in Quebec, Canada. Data on demographics, oncologic treatments, and complications, including NNE (defined as grade ≥ 2 diarrhea with radiologic ileocolitis) were extracted. RESULTS: A total of 223 patients were included, 82.9% of patients had stage III colorectal cancer, 54.3% received CAPOX, and 40.8% mFOLFOX6. NNE occurred in 12.4% of patients treated with CAPOX versus 1.1% with mFOLFOX6 (odds ratio [OR] 12.736, P = .002). All NNE were grade 3 to 4 events and required hospitalization. The median time to CAPOX-induced NNE onset was 36 days after the first chemotherapy dose. Risk factors for NNE included CAPOX use (OR [vs. mFOLFOX6] OR 12.736, P = .002) and age over 65 years (OR 4.214, P = .006). No difference in relapse-free survival was observed for stage III patients with versus without NNE (hazard ratio 0.247, P = .167). CONCLUSION: NNE is a significant complication of CAPOX, particularly in patients over 65 years. It occurs early in the treatment course, leads to a high rate of hospitalization, and necessitates careful patient selection and close monitoring during early cycles.