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
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Published in |
BMC Cancer, July 2016
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DOI | 10.1186/s12885-016-2491-y |
Pubmed ID | |
Authors |
Pashtoon M. Kasi, Daisuke Kotani, Michael Cecchini, Kohei Shitara, Atsushi Ohtsu, Ramesh K. Ramanathan, Howard S. Hochster, Axel Grothey, Takayuki Yoshino |
Abstract |
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. 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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 6 | 33% |
Canada | 2 | 11% |
Bosnia and Herzegovina | 1 | 6% |
Unknown | 9 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 11 | 61% |
Scientists | 6 | 33% |
Practitioners (doctors, other healthcare professionals) | 1 | 6% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 50 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 8 | 16% |
Other | 6 | 12% |
Student > Doctoral Student | 5 | 10% |
Student > Ph. D. Student | 5 | 10% |
Student > Master | 5 | 10% |
Other | 9 | 18% |
Unknown | 12 | 24% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 24 | 48% |
Nursing and Health Professions | 6 | 12% |
Agricultural and Biological Sciences | 4 | 8% |
Biochemistry, Genetics and Molecular Biology | 1 | 2% |
Arts and Humanities | 1 | 2% |
Other | 0 | 0% |
Unknown | 14 | 28% |