Katsuya Makihara1, Rino Fukui1, Hitomi Uchiyama1, Yasushi Shigeoka2, Akihiro Toyokawa3. 1. Department of Pharmacy, Yodogawa Christian Hospital, Osaka, Japan. 2. Department of Medical Oncology, Yodogawa Christian Hospital, Osaka, Japan. 3. Department of Surgery, Yodogawa Christian Hospital, Osaka, Japan.
Abstract
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%. 2019 Journal of Gastrointestinal Oncology. All rights reserved.
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%. 2019 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: T Doi; A Ohtsu; T Yoshino; N Boku; Y Onozawa; A Fukutomi; S Hironaka; W Koizumi; T Sasaki Journal: Br J Cancer Date: 2012-06-26 Impact factor: 7.640
Authors: A López-Pousa; J Rifà; A Casas de Tejerina; J L González-Larriba; C Iglesias; J A Gasquet; A Carrato Journal: Eur J Cancer Care (Engl) Date: 2010-01-19 Impact factor: 2.520