Evidence map›Paper›PMID 29211295›Full record

Trial reportCancer2018

Phase 2 study of treatment selection based on tumor thymidylate synthase expression in previously untreated patients with metastatic colorectal cancer: A trial of the ECOG-ACRIN Cancer Research Group (E4203).

Neal J Meropol, Yang Feng, Jean L Grem, Mary F Mulcahy, Paul J Catalano, John S Kauh, Michael J Hall, Joel N Saltzman, Thomas J George, Jeffrey Zangmeister and 4 more

Open access · bronzeAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.1field-weighted citation impact, top 46% of its field
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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Pharmacogenomics of 5-fluorouracil in colorectal cancer: review and update.Cellular oncology (Dordrecht, Netherlands) · 2020
    Review
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

14 authors at 12 institutions in 1 country.

Neal J MeropolCase Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio.
Yang FengDepartment of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts.
Jean L GremHematology/Oncology, University of Nebraska Medical Center, Omaha, Nebraska.ORCID 0000-0002-1672-9416
Mary F MulcahyDepartment of Medical Oncology, Northwestern University, Chicago, Illinois.
Paul J CatalanoDepartment of Biostatistics, Dana Farber Cancer Institute/Harvard Cancer Center, Boston, Massachusetts.
John S KauhDepartment of Medicine, Emory University, Atlanta, Georgia.
Michael J HallClinical Genetics and Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Joel N SaltzmanSeidman Cancer Center, Lake Health University Hospitals, Mentor, Ohio.
Thomas J GeorgeDivision of Hematology/Oncology University of Florida, Gainesville, Florida.
Jeffrey ZangmeisterHematology/Oncology, Mount Carmel Health Center West, Columbus, Ohio.
Elena G ChioreanHematology/Oncology, Indiana University, Indianapolis, Indiana.
Puneet S CheemaDepartment of Medical Oncology, Abbott-Northwestern Hospital, Minneapolis, Minnesota.
Peter J O'DwyerDepartment of Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
Al B BensonDepartment of Medical Oncology, Northwestern University, Chicago, Illinois.
Dana-Farber Cancer Institute · USNorthwestern University · USAbbott Northwestern Hospital · USCase Western Reserve University · USEmory University · USFox Chase Cancer Center · USIndiana University Health · USMount Carmel Health · USUniversity Hospitals Seidman Cancer Center · USUniversity of Florida · USUniversity of Nebraska Medical Center · USUniversity of Pennsylvania · US

Funding

Project-006U10CA180820 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer · 2014 to 2026
$167.6M
Statistics CoreU10CA180794 · NCI · DANA-FARBER CANCER INST · PI PAUL J CATALANO, CONSTANTINE A. GATSONIS · 2014 to 2026
$111.2M
Metro-Minnesota Community Oncology Research Consortium (MMCORC)UG1CA189863 · NCI · PARK NICOLLET INSTITUTE · PI JOLEEN M HUBBARD, Yan Ji · 2014 to 2026
$43.2M
ECOG-ACRIN Biospecimen Bank to Support NCTNU24CA196172 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI STANLEY R. HAMILTON, Scott D Jewell · 2015 to 2026
$41.1M
Columbus NCORP RFA-CA-18-016UG1CA189954 · NCI · COLUMBUS COMMUNITY CLINICAL ONCOLOGY PRG · PI Aruna Gowda, Malolan S Rajagopalan · 2014 to 2026
$9.8M
CWRU Case Comprehensive Cancer Center NCTN Lead Academic Participating SiteU10CA180853 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI GERDS, AARON THOMAS, MACHTAY, MITCHELL · 2014 to 2018
$6.2M
Vanderbilt Network Lead Academic Participating Site for the NCTNUG1CA233270 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kristen Keon Ciombor · 2019 to 2026
$3.5M
Hutchinson Center as Lead Academic Participating Site (U10)U10CA180828 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI APPELBAUM, FREDERICK · 2014 to 2018
$3.0M
Winship Cancer Institute, National Clinical Trials Network Lead Academic ParticipU10CA180864 · NCI · EMORY UNIVERSITY · PI BEITLER, JONATHAN, RAMALINGAM, SURESH S · 2014 to 2018
$2.9M
Vanderbilt Network Lead Academic Participating Site for the NCTNU10CA180847 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERLIN, JORDAN D · 2014 to 2018
$2.6M
Building upon a tradition of excellence. The NCTN at Indiana UniversityU10CA180795 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI MILLER, KATHY D. · 2014 to 2018
$2.6M
NCI NIH HHS U10 CA180794NCI NIH HHS U10 CA180795NCI NIH HHS U10 CA180820NCI NIH HHS U10 CA180828NCI NIH HHS U10 CA180847NCI NIH HHS U10 CA180853NCI NIH HHS U10 CA180864NCI NIH HHS U24 CA196172NCI NIH HHS UG1 CA189863NCI NIH HHS UG1 CA189954NCI NIH HHS UG1 CA233270
6 · The paper itself

Abstract

backgroundThe authors hypothesized that patients with metastatic colorectal cancer (mCRC) who had tumors with low thymidylate synthase (TS-L) expression would have a higher response rate to combined 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab (FOLFOX/Bev) than those with high TS (TS-H) expression and that combined irinotecan and oxaliplatin (IROX) plus bevacizumab (IROX/Bev) would be more effective than FOLFOX/Bev in those with TS-H tumors.

methodsTS protein expression was determined in mCRC tissue. Patients who had TS-L tumors received FOLFOX/Bev, and those who had TS-H tumors were randomly assigned to receive either FOLFOX/Bev or IROX/Bev. The primary endpoint was the response rate (complete plus partial responses).

resultsIn total, 211 of 247 patients (70% TS-H) were registered to the treatment phase. Efficacy analyses included eligible patients who had started treatment (N = 186). The response rates for patients who received IROX/Bev (TS-H), FOLFOX/Bev (TS-H), and FOLFOX/Bev (TS-L) were 33%, 38%, and 49%, respectively (P = nonsignificant). The median progression-free survival (PFS) was 10 months (95% confidence interval [CI], 9-12 months; 10 months in the IROX/Bev TS-H group, 9 months in the FOLFOX/Bev TS-H group, and 13 months in the FOLFOX/Bev TS-L group). The TS-L group had improved PFS compared with the TS-H group that received FOLFOX/Bev (hazard ratio, 1.6; 95% CI, 1.0%-2.4%; P = .04; Cox regression). The median overall survival (OS) was 22 months (95% CI, 20 29 months; 18 months in the IROX/Bev TS-H group, 21 months in the FOLFOX/Bev TS-H group, and 32 months in the TS-L group). OS comparisons for the 2 TS-H arms and for the FOLFOX/Bev TS-H versus TS-L arms were not significantly different.

conclusionsTS expression was prognostic: Patients with TS-L tumors who received FOLFOX/Bev had a longer PFS than those with TS-H tumors, along with a trend toward longer OS. Patients with TS-H tumors did not benefit more from IROX/Bev than from FOLFOX/Bev. Cancer 2018;124:688-97. © 2017 American Cancer Society.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBevacizumabColorectal NeoplasmsFemaleFluorouracilHumansImmunohistochemistryKaplan-Meier EstimateLeucovorinMaleMiddle AgedNeoplasm MetastasisOxaliplatinBevacizumabFluorouracilLeucovorinOxaliplatinThymidylate Synthase5-fluorouracilbevacizumabcolorectal canceririnotecanoxaliplatinpredictive factorsprognostic factorsthymidylate synthase

Identifiers

PMID29211295
PMCPMC6226304
OpenAlexW2773324414

What OpenQuestion holds

Textmetadata
LicenceTDM
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Registered trials

None linked

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.