Evidence mapPaperPMID 36077758Full record

ArticleCancers2022

Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies.

Makoto Ohno, Chifumi Kitanaka, Yasuji Miyakita, Shota Tanaka, Yukihiko Sonoda, Kazuhiko Mishima, Eiichi Ishikawa, Masamichi Takahashi, Shunsuke Yanagisawa, Ken Ohashi and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Glioblastoma Metabolism: Insights and Therapeutic Strategies.International journal of molecular sciences · 2023
    Review
  9. Review
  10. Article
  11. Article
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

12 authors at 6 institutions in 1 country.

Makoto OhnoDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.ORCID 0000-0001-8031-4306
Chifumi KitanakaDepartment of Molecular Cancer Science, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.
Yasuji MiyakitaDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Shota TanakaDepartment of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Yukihiko SonodaDepartment of Neurosurgery, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.
Kazuhiko MishimaDepartment of Neuro-Oncology/Neurosurgery, International Medical Center, Saitama Medical University, Hidaka 350-1298, Japan.
Eiichi IshikawaDepartment of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba 350-8576, Japan.
Masamichi TakahashiDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.ORCID 0000-0001-8792-1993
Shunsuke YanagisawaDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Ken OhashiDepartment of General Internal Medicine, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Motoo NaganeDepartment of Neurosurgery, Kyorin University Faculty of Medicine, Mitaka 181-8611, Japan.ORCID 0000-0002-0018-1652
Yoshitaka NaritaDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.ORCID 0000-0003-4303-6006
Yamagata University · JPKyorin University · JPSaitama Medical University · JPThe University of Tokyo · JPTokyo National Hospital · JPUniversity of Tsukuba · JP

Funding

Japan Agency for Medical Research and Development 21ck0106623h0002
6 · The paper itself

Abstract

Glioblastoma (GBM) inevitably recurs due to a resistance to current standard therapy. We showed that the antidiabetic drug metformin (MF) can induce the differentiation of stem-like glioma-initiating cells and suppress tumor formation through AMPK-FOXO3 activation. In this study, we design a phase I/II study to examine the clinical effect of MF. We aim to determine a recommended phase II MF dose with maintenance temozolomide (TMZ) in patients with newly diagnosed GBM who completed standard concomitant radiotherapy and TMZ. MF dose-escalation was planned using a 3 + 3 design. Dose-limiting toxicities (DLTs) were assessed during the first six weeks after MF initiation. Three patients were treated with 1500 mg/day MF and four patients were treated with 2250 mg/day MF between February 2021 and January 2022. No DLTs were observed. The most common adverse effects were appetite loss, nausea, and diarrhea, all of which were manageable. Two patients experienced tumor progression at 6.0 and 6.1 months, and one died 12.2 months after initial surgery. The other five patients remained stable at the last follow-up session. The MF dose of up to 2250 mg/day combined with maintenance TMZ appeared to be well tolerated, and we proceeded to a phase II study with 2250 mg/day MF.

Indexed as

dose-escalationmetforminnewly diagnosed glioblastomaphase Itemozolomide

Identifiers

PMID36077758
PMCPMC9454846
OpenAlexW4293776731

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.