Evidence map›Paper›PMID 27412464›Full record

ArticleBMC cancer2016

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.

Pashtoon M Kasi, Daisuke Kotani, Michael Cecchini, Kohei Shitara, Atsushi Ohtsu, Ramesh K Ramanathan, Howard S Hochster, Axel Grothey, Takayuki Yoshino

Abstract readComparative StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  16. Efficacy and safety of trifluridine/tipiracil plus ramucirumab in comparison with trifluridine/tipiracil monotherapy for patients with advanced gastric cancer-single institutional experience.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Pashtoon M KasiDivision of Medical Oncology, Mayo Clinic, 200 First St SW, Rochester, 55905, MN, USA. kasi.pashtoon@mayo.edu.
Daisuke KotaniDepartment of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Michael CecchiniDivision of Medical Oncology, Yale Cancer Center, New Haven, CT, USA.
Kohei ShitaraDepartment of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Atsushi OhtsuDepartment of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Ramesh K RamanathanDivision of Medical Oncology, Mayo Clinic, Scottsdale, Arizona, USA.
Howard S HochsterDivision of Medical Oncology, Yale Cancer Center, New Haven, CT, USA.
Axel GrotheyDivision of Medical Oncology, Mayo Clinic, 200 First St SW, Rochester, 55905, MN, USA.
Takayuki YoshinoDepartment of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
NCATS NIH HHS UL1 TR001863
6 · The paper itself

Abstract

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/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.

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.

Indexed as

AgedAge FactorsAntineoplastic AgentsChemotherapy-Induced Febrile NeutropeniaClinical Trials, Phase III as TopicCohort StudiesColorectal NeoplasmsDisease-Free SurvivalDose-Response Relationship, DrugDrug CombinationsDrug Resistance, NeoplasmFemaleHumansJapanKaplan-Meier EstimateMaleAntineoplastic AgentsDrug CombinationsPyrrolidinesThymineTrifluridinetrifluridine tipiracil drug combinationUracilBiomarkerChemotherapy induced neutropeniaColorectal CancerHematological toxicityPharmacogenomicsPredictive biomarkerPrognostic markerTAS-102

Identifiers

PMID27412464
PMCPMC4944251

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.