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- Title
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.
- Authors
Kasi, Pashtoon M.; Daisuke Kotani; Cecchini, Michael; Kohei Shitara; Atsushi Ohtsu; Ramanathan, Ramesh K.; Hochster, Howard S.; Grothey, Axel; Takayuki Yoshino; Kotani, Daisuke; Shitara, Kohei; Ohtsu, Atsushi; Yoshino, Takayuki
- Abstract
<bold>Background: </bold>TAS-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.<bold>Methods: </bold>CIN-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/mm(3)). 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.<bold>Results: </bold>Our 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.<bold>Conclusions: </bold>Our 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.
- Subjects
JAPAN; UNITED States; COLON cancer patients; NEUTROPENIA; LOG-rank test; CANCER chemotherapy; COHORT analysis; NEUTROPHILS; AGE distribution; ANTINEOPLASTIC agents; COMBINATION drug therapy; CLINICAL trials; COLON tumors; COMPARATIVE studies; DRUG resistance in cancer cells; DOSE-effect relationship in pharmacology; HETEROCYCLIC compounds; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; PROGNOSIS; RECTUM tumors; RESEARCH; RESEARCH funding; EVALUATION research; KAPLAN-Meier estimator; DEOXYRIBONUCLEOSIDES; THERAPEUTICS
- Publication
BMC Cancer, 2016, Vol 16, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-016-2491-y