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A randomized, double-blind, placebo-controlled trial of metformin in reducing progression among men on expectant management for low-risk prostate cancer: The MAST (Metformin Active Surveillance Trial) study.

2024· article· en· W4399452333 on OpenAlexaffabout
Neil Fleshner, Rui Bernardino, Katherine Lajkosz, Fred Saad, Jonathan I. Izawa, Darrel Drachenberg, Jeff Saranchuk, Simon Tanguay, Ricardo Rendon, Michael Leveridge, Bobby Shayegan, Adrian Fairey, Jessica Cockburn, Doron Berlin, Robert J. Hamilton, Tiiu Sildva, Rodney H. Breau, Patrick O. Richard, Laurence H. Klotz, Anthony M. Joshua

Bibliographic record

VenueJournal of Clinical Oncology · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolism, Diabetes, and Cancer
Canadian institutionsSunnybrook Health Science CentreUniversity of ManitobaSt. Joseph’s Healthcare HamiltonMcMaster UniversityQueen's UniversityMcGill University Health CentreHealth Sciences CentreOttawa HospitalUniversity Health NetworkCancerCare ManitobaUniversity of TorontoWestern UniversityHôpital FleurimontPrincess Margaret Cancer CentreCentre Hospitalier de l’Université de MontréalDalhousie University
Fundersnot available
KeywordsMedicineMetforminProstate cancerTolerabilityProstatectomyClinical endpointProstateInternal medicinePlaceboProstate-specific antigenRandomized controlled trialCancerOncologyUrologyGynecologyAdverse effectPathologyInsulin

Abstract

fetched live from OpenAlex

LBA5002 Background: Active Surveillance (AS) involves vigilant monitoring of selected prostate cancer (PCa) patients, with radical treatment initiation upon significant disease progression. AS eligibility varies, generally including low-risk PCa men. Metformin, a widely-used oral hypoglycemic agent, is known for its excellent tolerability and efficacy in diabetes management. Extensive preclinical data suggested that metformin may slow PCa progression. The purpose of this study is to examine the effect of metformin on the rates of progression among men with low-risk localized PCa on AS. Methods: A randomized double blind placebo controlled trial was carried out in 14 centres across Canada.Eligible patients had biopsy-proven, low-risk, localized PCa diagnosed within the past 6 months, with a Gleason score of <6 observed in ≤1/3 of the total cores, less than 50% positivity in any one core, a PSA level of ≤10 ng/ml, and a clinical stage between T1c-T2a. Additionally, they chose active surveillance as their primary treatment. Subjects that met eligibility criteria were randomly assigned (1:1) to receive metformin 850 mg BID or placebo for 3 years. All patients underwent repeat prostate biopsy at 18 and 36 months. The primary endpoint indicated was time to progression, defined as the earliest occurrence of primary PCa therapy (e.g., prostatectomy, radiation, hormonal therapy) or pathological progression (>1/3 of total cores involved, at least 50% of any one core involved, or Gleason pattern 4 or higher). Results: In our cohort of 407 patients, 204 were administered metformin, and 203 received a placebo. The median age of the overall cohort was 63 years. Out of the total 407 patients, 141 experienced disease progression. There was no statistically significant difference in progression-free survival (PFS) observed between patients treated with metformin and those receiving placebo (p=0.63). Conclusions: Despite tantalizing preclinical and epidemiological data, metformin consumption does not alter rates of progression among men with low risk PCa on AS. Clinical trial information: NCT01864096 .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.007
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0010.000
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0070.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.051
GPT teacher head0.435
Teacher spread0.384 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations15
Published2024
Admission routes2
Has abstractyes

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