Article Abstract

Decreased percentage of neutrophil is a predict factor for the efficacy of trifluridine and tipiracil hydrochloride for pretreated metastatic colorectal cancer

Authors: Katsuya Makihara, Rino Fukui, Hitomi Uchiyama, Yasushi Shigeoka, Akihiro Toyokawa


Background: The concentration of trifluridine in tumor DNA was strongly correlated with that of white blood cells in tumor-bearing nude mice administered trifluridine-tipiracil (TAS-102). Further, a phase I study of TAS-102 in patients with advanced solid tumors showed a significant correlation between decreased neutrophil count and the area under the concentration-time curve of trifluridine. Herein, we aimed to evaluate the association of decreased neutrophil count with the efficacy of TAS-102.
Methods: We retrospectively analyzed 40 patients with pretreated metastatic colorectal cancer who received TAS-102 at Yodogawa Christian Hospital between June 2014 and May 2018. To evaluate the association between the efficacy of TAS-102 and decreased neutrophil count, patients were grouped into 4 categories according to the decrease of neutrophil count during the first cycle of TAS-102 as follows: Category A, <25%; B, 25% to <50%; C, 50% to <75%; D, ≥75%.
Results: The rate of overall survival (OS) was significantly different between Category A and B (median: 4.1 vs. 10.1 months; P=0.04), between Category A and C (median: 4.1 vs. 10.5 months; P=0.04), and between Category A and D (median: 4.1 vs. 15.6 months; P=0.04). In the multivariate analyses, a ≥25% decrease of neutrophils [hazard ratio (HR): 0.28; 95% confidence interval (CI): 0.12–0.72; P=0.01] and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 (HR: 3.79, 95% CI: 1.04–11.2; P=0.04) were independent prognostic factors for OS.
Conclusions: Decreased neutrophil count is a predict factor for the efficacy of TAS-102. TAS-102 treatment may be ineffective in patients with a decreased neutrophil count of <25%.

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