Incidence and risk factors of non-neutropenic enterocolitis with adjuvant capecitabine and oxaliplatin chemotherapy in colorectal cancer.

116 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, cases of severe diarrhea associated with radiologic ileocolitis (non-neutropenic enterocolitis NNE), and related hospitalizations have not been well described. Methods: This is a retrospective cohort study of patients treated with adjuvant CAPOX, mFOLFOX6 (infusional 5-fluorouracil, leucovorin and oxaliplatin), and capecitabine for stage II to IV colorectal cancer between 2015 and 2023 at two academic hospitals in Quebec, Canada. Data on demographics, oncologic treatments, and complications were extracted to assess the real-world incidence of NNE (defined as grade ≥ 2 diarrhea per CTCAE v5.0 with radiologic ileocolitis). Chi-square tests were performed to compare incidence of NNE by chemotherapy received and identify risk factors for NNE. 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. Grade ≥ 2 diarrhea was more frequent with CAPOX than mFOLFOX6 and capecitabine, and NNE occurred in 12.4% of patients treated with CAPOX versus 1.1% with mFOLFOX6. All NNE were grade 3-4 events and required hospitalization. The median time between the first dose of chemotherapy and CAPOX-induced was 36. Risk factors for NNE included CAPOX use (OR versus mFOLFOX6 12.658, p = 0,004) and age over 65 years (OR 4.214, p = 0.006). No difference in relapse-free survival was observed for stage III patients with versus without NNE (HR 0.247, p = 0.167). Conclusions: NNE is a significant complication of CAPOX, especially among 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. Incidence and characteristics of gastrointestinal toxicities. CAPOX (n = 121)n (%) mFOLFOX6 (n = 91)n (%) Capecitabine (n = 11)n (%) OR* 95% CI, p value Diarrhea gr ≥ 2 36 (29.8) 3 (3.3) 0 (0.0) 12.424 3.686-41.868, p < 0.001 Hospitalization for diarrhea 23 (19.0) 3 (3.3) 0 (0.0) 6.884 1.998-23.720, p < 0.001 NNE 15 (12.4) 1 (1.1) 0 (0.0) 12.736 1.650-98.304, p = 0.002 Grade 3 14/15 (93.3) 1/1 (100.0) N/A Grade 4 1/15 (6.7) 0/1 (0.0) N/A Time between first day of chemotherapy and NNE (IQR) (days) 36 19-39 77 N/A N/A N/A, p = 0.125 Hospitalization for NNE 15/15 (100.0) 1/1 (100) N/A N/A, p = 1.000 *As there was no event with capecitabine, odds ratios were calculated only between CAPOX and mFOLFOX6 groups. IQR: interquartile range; N/A : not applicable; NNE: non-neutropenic enterocolitis.