Evidence mapPaperPMID 29948021Full record

Trial reportCancer chemotherapy and pharmacology2018

A pharmacodynamic study of sirolimus and metformin in patients with advanced solid tumors.

Amikar Sehdev, Theodore Karrison, Yuanyuan Zha, Linda Janisch, Michelle Turcich, Ezra E W Cohen, Michael Maitland, Blase N Polite, Thomas F Gajewski, Ravi Salgia and 5 more

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Cancer chemotherapy and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Metformin and Cancer, an Ambiguanidous Relationship.Pharmaceuticals (Basel, Switzerland) · 2022
    Review
  8. Review
  9. Review
  10. Metformin: A Possible Option in Cancer Chemotherapy.Analytical cellular pathology (Amsterdam) · 2020
    Review
  11. Review
  12. Review
  13. 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

15 authors at 2 institutions in 1 country.

Amikar SehdevSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA. asehdev@iupui.edu.
Theodore KarrisonDepartment of Public Health Sciences, University of Chicago, Chicago, IL, USA.
Yuanyuan ZhaSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Linda JanischSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Michelle TurcichSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Ezra E W CohenSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Michael MaitlandSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Blase N PoliteSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Thomas F GajewskiSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Ravi SalgiaSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Navin PintoSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Marc B BissonnetteSection of Gastroenterology, Department of Medicine, University of Chicago, Chicago, IL, USA.
Gini F FlemingSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Mark J RatainSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Manish R SharmaSection of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA. msharma@bsd.uchicago.edu.
University of Chicago · USChicago Department of Public Health · US

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · 1985 to 2025
$29.5M
ULTRASTRUCTURE AND CYTOMORPHOLOGY COREP30DK042086 · NIDDK · UNIVERSITY OF CHICAGO · 1990 to 2025
$12.3M
NCI NIH HHS P30 CA014599NIDDK NIH HHS P30 DK042086
6 · The paper itself

Abstract

backgroundSirolimus is a mammalian target of rapamycin (mTOR) inhibitor. Metformin may potentiate mTOR inhibition by sirolimus while mitigating its adverse effects. We conducted a pilot study to test this hypothesis.

methodsPatients with advanced solid tumor were treated with sirolimus for 7 days followed by randomization to either sirolimus with metformin (Arm A) or sirolimus (Arm B) until day 21. From day 22 onwards, all patients received sirolimus and metformin. The primary aim was to compare the change in phospho-p70S6K (pp70S6K) in peripheral blood mononuclear cells (PBMC) from day 8 to day 22 using a two-sample t test. Secondary aims were objective response rate, toxicity, and other serum pharmacodynamic biomarkers (e.g., fasting glucose, triglycerides, insulin, C-peptide, IGF-1, IGF-1R, IGF-BP, and leptin).

results24 patients were enrolled, with 18 evaluable for the primary endpoint. There was no significant difference in mean change in pp70S6K in arm A vs. arm B (- 0.12 vs. - 0.16; P = 0.64). Similarly, there were no significant differences in other serum pharmacodynamic biomarkers. There were no partial responses. There were no dose-limiting or unexpected toxicities.

conclusionsAdding metformin to sirolimus, although well tolerated, was not associated with significant changes in pp70S6K in PBMC or other serum pharmacodynamic biomarkers. IMPACT: Combining metformin with sirolimus did not improve mTOR inhibition.

Indexed as

AdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorDrug SynergismFemaleHumansLeukocytes, MononuclearMaleMetforminMiddle AgedNeoplasmsPhosphorylationPilot ProjectsBiomarkers, TumorMetforminMTOR protein, humanRibosomal Protein S6 Kinases, 70-kDaSirolimusTOR Serine-Threonine KinasesMetforminP70S6K and mTORPharmacodynamicsSirolimusSolid tumors

Identifiers

PMID29948021
PMCPMC6739841
OpenAlexW2805648050

What Socratic 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 Socratic graph.