Evidence map›Paper›PMID 26033830›Full record

Trial reportCancer2015

Randomized phase 2 trial of erlotinib in combination with high-dose celecoxib or placebo in patients with advanced non-small cell lung cancer.

Karen L Reckamp, Marianna Koczywas, Mihaela C Cristea, Jonathan E Dowell, He-Jing Wang, Brian K Gardner, Ginger L Milne, Robert A Figlin, Michael C Fishbein, Robert M Elashoff and 1 more

Open access · bronzeAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 6 pooled it
3.7field-weighted citation impact, top 8% 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

23 citing papers in PubMed, 6 syntheses or guidelines pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Celecoxib Inhibits Hepatocellular Carcinoma Cell Growth and Migration by Targeting PNO1.Medical science monitor : international medical journal of experimental and clinical research · 2019
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 1 country.

Karen L ReckampDepartment of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California.
Marianna KoczywasDepartment of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California.
Mihaela C CristeaDepartment of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California.
Jonathan E DowellDepartment of Medicine, Veterans Affairs North Texas Healthcare System, University of Texas Southwestern Medical Center, Dallas, Texas.
He-Jing WangDepartment of Biomathematics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
Brian K GardnerDepartment of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
Ginger L MilneDepartments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee.
Robert A FiglinDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Michael C FishbeinDepartment of Pathology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
Robert M ElashoffDepartment of Biomathematics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
Steven M DubinettDepartments of Medicine and Pathology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
University of California, Los Angeles · USCity Of Hope National Medical Center · USCedars-Sinai Medical Center · USThe University of Texas Southwestern Medical Center · USVanderbilt University · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
University of Florida Older Americans Independence Center (OAIC)P30AG028740 · NIA · UNIVERSITY OF FLORIDA · PI CHRISTIAAN LEEUWENBURGH · 2007 to 2026
$22.8M
Oncology Research Career Development ProgramK12CA001727 · NCI · CITY OF HOPE NATIONAL MEDICAL CENTER · PI MORTIMER, JOANNE E. · 1992 to 2024
$14.6M
UCLA SPORE IN LUNG CANCERP50CA090388 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2001 to 2008
$13.0M
UCLA OLDER AMERICANS INDEPENDENCE CENTERP30AG028748 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MOORE, ALISON AHERN · 2006 to 2017
$9.8M
NCI NIH HHS K12 CA001727NCI NIH HHS K12 CA01727NCI NIH HHS P30 CA033572NCI NIH HHS P30CA033572NCI NIH HHS P50 CA090388NIA NIH HHS 5P30AG028748NIA NIH HHS P30 AG028740NIA NIH HHS P30 AG028748
6 · The paper itself

Abstract

backgroundCyclooxygenase 2 (COX-2)-dependent signaling represents a potential mechanism of resistance to therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. This is mediated in part through an EGFR-independent activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) by prostaglandin E2 (PGE2). PGE2 promotes downregulation of E cadherin and epithelial to mesenchymal transition. The current study investigated EGFR and COX-2 inhibition in patients with non-small cell lung cancer (NSCLC) and elevated baseline urinary metabolite of PGE2 (PGEM).

methodsPatients with stage IIIB/IV (AJCC 6th edition) NSCLC who progressed after at least 1 line of therapy or refused standard chemotherapy were randomized to receive erlotinib and celecoxib versus erlotinib and placebo. The primary endpoint was progression-free survival (PFS) with 80% power to detect a 50% improvement with a 1-sided significance level of .2 in the intent-to-treat and elevated baseline PGEM populations. Secondary endpoints included response rate, overall survival, and evaluation of molecular markers to assess targeting COX-2-related pathways and evaluate EGFR tyrosine kinase inhibitor resistance.

resultsA total of 107 patients were enrolled with comparable baseline characteristics. Among the patients treated with celecoxib, those with wild-type EGFR were found to have an increased PFS (3.2 months vs 1.8 months; P = .03). PFS was numerically improved among patients in the intent-to-treat group who received erlotinib and celecoxib compared with those treated with erlotinib and placebo (5.4 months vs 3.5 months; P = .33) and was increased in patients in the erlotinib and celecoxib arm with elevated baseline PGEM (5.4 months vs 2.2 months; P = .15). Adverse events were similar in both treatment arms.

conclusionsThe combination of erlotinib and celecoxib did not appear to improve outcomes in an unselected population, but selection by elevated baseline PGEM led to an increase in PFS with this combination. Patients with EGFR wild-type status may benefit from the combination of erlotinib and celecoxib.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCelecoxibDinoprostoneDisease-Free SurvivalDNA Mutational AnalysisDouble-Blind MethodErlotinib HydrochlorideFemaleGenes, erbB-1HumansImmunohistochemistryKaplan-Meier EstimateCelecoxibDinoprostoneErlotinib Hydrochloridecelecoxibcyclooxygenase 2 (COX-2)epidermal growth factor receptor (EGFR)erlotinibnon-small cell lung cancer (NSCLC)prostaglandin E2 (PGE2)

Identifiers

PMID26033830
PMCPMC4864011
OpenAlexW1604183045

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.