Prognostic impact and risk factors of severe neutropenia in the early phase of treatment with trifluridine-tipiracil for metastatic colorectal cancer patients: a single-center retrospective study.

Purpose: We aimed to identify the risk factors for severe neutropenia in the early phase of trifluridine-tipiracil (FTD/TPI) treatment, and their impact on overall survival (OS).

Methods: This single-center retrospective study included patients with unresectable metastatic colorectal cancer who were treated with FTD/TPI. The primary endpoint was OS, and the secondary endpoint was severe neutropenia during the first and second cycles of FTD/TPI. We assessed the association between outcomes and potential confounders using multivariate analysis.

Results: Of the 77 total patients, 33 developed severe neutropenia during the first and second treatment cycles. In Cox hazard analysis, the independent factors associated with OS were neutropenia ≥ grade 1 during cycles 1 and 2 (adjusted hazard ratio 0.43; 95% confidence interval (CI) 0.21-0.87), combined treatment with bevacizumab (0.47; 95% CI 0.27-0.83), number of metastatic organs ≥ 3 (2.15; 95% CI 1.22-3.82), and time since diagnosis of metastasis until commencement of FTD/TPI < 18 months (1.94; 95% CI 1.13-3.33). Severe neutropenia during cycles 1 and 2 was not associated with OS (0.75; 0.44-1.27). 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, 4.67; 95% CI, 1.38-15.80) and absolute neutrophil count (per 1000/μl, 0.47; 0.27-0.81).

Conclusion: The neutropenia ≥ grade 1 during cycles 1 and 2 of FTD/TPI is a predictor of favorable outcomes; however, the effect of severe neutropenia on OS was not clear. Renal impairment was also associated with severe neutropenia.