Evidence map›Paper›PMID 24861559›Full record

ArticleProstate cancer and prostatic diseases2014

A pilot 'window of opportunity' neoadjuvant study of metformin in localised prostate cancer.

A M Joshua, V E Zannella, M R Downes, B Bowes, K Hersey, M Koritzinsky, M Schwab, U Hofmann, A Evans, T van der Kwast and 5 more

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Prostate cancer and prostatic diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03031821 (A Randomized Phase 3 Trial of Metformin in Patients Initiating Androgen Deprivation Therapy as Prevention and Intervention of Metabolic Syndrome), which is not on this map. Cited by 50 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 4% 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.

NCT03031821 phase3terminatedstarted 2018, after this paper: background citation

A Randomized Phase 3 Trial of Metformin in Patients Initiating Androgen Deprivation Therapy as Prevention and Intervention of Metabolic Syndrome: The Prime Study

Ran2018Enrolled166Registered outcomes30Posted comparisons0ConditionsMetabolic Syndrome, Prostate CancerArmsMetformin, Placebo Oral Tablet
PMID 21933330PMID 20452916PMID 26633628PMID 9742977PMID 25017630PMID 23230096PMID 8569826PMID 25456737PMID 24412228PMID 25536258PMID 23918942PMID 15838067other papers from this trial
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3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 76 citations in OpenAlex.

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  4. Bioactivity and prostate tissue distribution of metformin in a preprostatectomy prostate cancer cohort.European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) · 2018
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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

15 authors at 4 institutions in 2 countries.

A M JoshuaPrincess Margaret Cancer Centre, Toronto, ON, Canada.
V E ZannellaPrincess Margaret Cancer Centre, Toronto, ON, Canada.
M R Downes1] Princess Margaret Cancer Centre, Toronto, ON, Canada [2] Department of Pathology, University Health Network, Toronto, ON, Canada.
B BowesPrincess Margaret Cancer Centre, Toronto, ON, Canada.
K HerseyPrincess Margaret Cancer Centre, Toronto, ON, Canada.
M KoritzinskyPrincess Margaret Cancer Centre, Toronto, ON, Canada.
M Schwab1] Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany [2] University of Tübingen, Stuttgart, Germany.
U Hofmann1] Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany [2] University of Tübingen, Stuttgart, Germany.
A Evans1] Princess Margaret Cancer Centre, Toronto, ON, Canada [2] Department of Pathology, University Health Network, Toronto, ON, Canada.
T van der Kwast1] Princess Margaret Cancer Centre, Toronto, ON, Canada [2] Department of Pathology, University Health Network, Toronto, ON, Canada.
J Trachtenberg1] Princess Margaret Cancer Centre, Toronto, ON, Canada [2] Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany [3] University of Tübingen, Stuttgart, Germany.
A Finelli1] Princess Margaret Cancer Centre, Toronto, ON, Canada [2] Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany [3] University of Tübingen, Stuttgart, Germany.
N Fleshner1] Princess Margaret Cancer Centre, Toronto, ON, Canada [2] Division of Urology, Department of Surgery, University Health Network, Toronto, ON, Canada.
J Sweet1] Princess Margaret Cancer Centre, Toronto, ON, Canada [2] Department of Pathology, University Health Network, Toronto, ON, Canada.
M PollakJewish General Hospital, Montreal, QC, Canada.
Princess Margaret Cancer Centre · CADr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology · DEUniversity Health Network · CAJewish General Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetformin is an inhibitor of complex 1 in the respiratory chain, and is widely used to reduce insulin resistance. It has also been described to have pleotropic effects including via AMPK on inhibiting the mTOR kinase. Pre-clinical and epidemiological studies suggest an ability to modulate disease evolution in prostate cancer. In this study, we aimed to (i) demonstrate safety and tolerability of neoadjuvant metformin administration and (ii) document changes in proliferative (Ki67) and AMPK-related signalling indices between matching biopsies and prostatectomies

methodsMen were treated in a single-arm 'window of opportunity' study between their decision to undergo radical prostatectomy and the operation itself. Forty patients were planned but only 24 patients were enrolled owing to slow accrual. Twenty-one patients were evaluable for pathological outcomes and 22 for serum metabolic indices. Metformin was given at doses to 500 mg t.i.d. Ki67 index was calculated using the Aperio-positive pixel count algorithm, whereas immunohistochemical measurements were by consensus H-Score. Comparative statistics were analysed by students t-tests and/or Wilcoxon matched pairs signed rank test.

resultsBaseline characteristics included median PSA 6 ng ml(-1) (3.22-36.11 ng ml(-1)). Median duration of drug treatment was 41 days (18-81). Treatment was well tolerated with only three patients developing G3/4 toxicities. In a per patient and per tumour analyses, metformin reduced the Ki67 index by relative amounts of 29.5 and 28.6 % (P=0.0064 and P=0.0042) respectively. There was also a significant decrease in P-4EBP1 staining (P<0.001) but no change in P-AMPK or P-ACC. There were no correlations between any metabolic, morphometric or cancer-related serum indices. There was a trend towards PSA reduction (P=0.08). The study is limited by small patient numbers and tumour heterogeneity.

conclusionsNeoadjuvant metformin is well tolerated prior to radical prostatectomy. Data to date indicate promising effects on metabolic and tissue proliferation and signalling parameters.

Indexed as

AgedAntineoplastic AgentsBiomarkers, TumorBiopsyHumansMaleMetforminMiddle AgedNeoadjuvant TherapyNeoplasm GradingNeoplasm StagingPilot ProjectsProstatic NeoplasmsAntineoplastic AgentsBiomarkers, TumorMetformin

Identifiers

PMID24861559
OpenAlexW2082705146

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.