Risk factors and prognostic impact of severe neutropenia in the first cycle of trifluridine-tipiracil for metastatic colorectal cancer patients: A single-center retrospective study

Purpose: Several studies have reported that chemotherapy-induced neutropenia in the early phase contributes to better outcomes of patients treated with trifluridine-tipiracil (FTD/TPI) treatment. We aimed to identify the risk factors for severe neutropenia during FTD/TPI treatment, and their impacts on overall survival (OS). Methods: This single-center retrospective study included patients with unresectable metastatic colorectal cancer who were treated with FTD/TPI between May 2014 and April 2023. The primary endpoint was OS, and the secondary endpoint was severe neutropenia in the first cycle of FTD/TPI. We assessed the association between outcomes and potential confounders using multivariate analysis. Results: Of the 85 total patients, 24 developed severe neutropenia during the first treatment cycle. The risk of severe neutropenia adjusted for initial dose reduction was defined as renal impairment with creatinine clearance (Ccr) of < 60 mL/min (adjusted odds ratio, 3.83; 95% confidence interval, 1.29–12.43) and absolute neutrophil count (per 1,000/µL: 0.54, 0.32–0.85). In our Cox hazard analysis, the independent factors associated with OS were neutropenia ≥ Grade 1 in cycle 1 or 2 (adjusted hazard ratio, 0.37; 95% CI 0.19–0.72), combined treatment with bevacizumab (0.55; 95% CI 0.32–0.94) and number of metastatic organs (1.58; 1.21–2.07). Severe neutropenia in cycle 1 was not associated with OS (1.13, 0.62–2.04). Conclusion: Renal impairment was associated with the severe neutropenia treated using FTD/TPI. It remains unclear whether severe neutropenia in the early phases of FTD/TPI treatment is a predictor of favorable outcomes.