Chemotherapy induced neutropenia at 1-month mark is a predictor of overall survival in patients receiving TAS-102 for refractory metastatic colorectal cancer: a cohort study

BMC Cancer

Research Article

Atsushi Ohtsu¹  Takayuki Yoshino¹  Daisuke Kotani¹  Kohei Shitara¹  Axel Grothey²  Pashtoon M. Kasi²  Ramesh K. Ramanathan³  Howard S. Hochster⁴  Michael Cecchini⁴ 

[1] Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan;Division of Medical Oncology, Mayo Clinic, 200 First St SW, 55905, Rochester, MN, USA;Division of Medical Oncology, Mayo Clinic, Scottsdale, Arizona, USA;Division of Medical Oncology, Yale Cancer Center, New Haven, CT, USA;

关键词: TAS-102;    Colorectal Cancer;    Chemotherapy induced neutropenia;    Hematological toxicity;    Biomarker;    Predictive biomarker;    Prognostic marker;    Pharmacogenomics;   

DOI  :  10.1186/s12885-016-2491-y

 received in 2016-03-14, accepted in 2016-06-28,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundTAS-102 (trifluridine and tipiracil hydrochloride; a novel combination oral nucleoside anti-tumor agent) has recently received regulatory approval for patients with refractory metastatic colorectal cancer (mCRC). Internal review of data at a single-institution showed a trend towards better overall survival (OS) for patients who experienced chemotherapy-induced neutropenia at 1-month (CIN-1-month). To explore this finding further, a cohort study was designed based on outcome data from three centers in United States and one from Japan.MethodsCIN-1-month after starting TAS-102 was defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 as a neutrophil count decrease of ≥ grade 2 (absolute neutrophil count < 1500/mm3). Patients had confirmed mCRC that was refractory to standard therapies. Patient demographics and clinical characteristics were compared between patients with CIN-1-month (CIN-1-month positive) versus those who did not have CIN-1-month (CIN-1-month negative); with the median progression-free survival (PFS) and OS were calculated using the Kaplan-Meier method, and differences evaluated using the Log-rank test.ResultsOur cohort study had a total of 149 patients with data regarding their neutrophil assessment at 1-month mark. Patients who developed ≥ grade 2 CIN-1-month had a both longer PFS (median 3.0 months versus 2.4 months; Log-rank P-value = 0.01), as well as OS (14.0 versus 5.6 months; Log-rank P-value < 0.0001). Only CIN-1-month (adjusted HR: 0.21 (95 % CI: 0.11–0.38) and higher baseline CEA levels (adjusted HR: 2.00 (95 % CI: 1.22–3.35) were noted to be independent predictors of OS. Furthermore, the CIN-1-month was noted to be a statistically significantly predictor of OS over a wide range of cutoffs.ConclusionsOur observations are novel and hypothesis generating. Neutropenia after starting TAS-102 was associated with better prognosis in patients with refractory mCRC. It can be postulated that the dosage of TAS-102 potentially may need to be increased to achieve better outcomes in patients not experiencing any neutropenia. Further pharmacologic investigations should help elucidate these issues.

【 授权许可】

CC BY   
© The Author(s). 2016