CoChat
Sign Up
Cited by 361

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial

Kordes, Sil, Pollak, Michael N, Zwinderman, Aeilko H, Mathôt, Ron A, Weterman, Mariëtte J, Beeker, Aart, Punt, Cornelis J, Richel, Dick J, Wilmink, Johanna W·2015·The Lancet Oncology
DOI 10.1016/s1470-2045(15)00027-3
Open this paper in CoChat — free account

Abstract

Background In preclinical work and retrospective population studies, the anti-diabetic drug metformin has been associated with antineoplastic activity and decreased burden of many cancers, including pancreatic cancer. There is therefore interest in the hypothesis that this drug might be repurposed for indications in oncology. We aimed to assess the efficacy of the addition of metformin to a standard systemic therapy in patients with advanced pancreatic cancer, and provide the first report of a clinical trial with a survival endpoint of metformin for an oncological indication. Methods We did this double-blind, randomised, placebo-controlled phase 2 trial at four centres in the Netherlands. Patients aged 18 years or older with advanced pancreatic cancer were randomly assigned (1:1), via a permutated computer-generated block allocation scheme (block size of six) to receive intravenous gemcitabine (1000 mg/m(2)) on days 1, 8, and 15 every 4 weeks and oral erlotinib (100mg) once daily in combination with either oral metformin or placebo twice daily. Metformin dose was escalated from 500 mg (in the first week) to 1000 mg twice daily in the second week. Randomisation was stratified by hospital, diabetes status, and tumour stage. The primary endpoint was overall survival at 6 months in the intention-to-treat population. This trial is complete and is registered with ClinicalTrials.gov, number NCT01210911. Findings Between May 31, 2010, and Jan 3, 2014, we randomly assigned 121 patient…

Overview

Integrity signals

Registry

Crossref · 10.1016/s1470-2045(15)00027-3

Cites

11 of 11 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

Show all 11 references

Research works printed but not linked: 25

  1. Pollak, 2014, Overcoming drug development bottlenecks with repurposing: repurposing biguanides to target energy metabolism for cancer treatment, Nat Med, 20, 591, 10.1038/nm.3596 · DOI
  2. DeCensi, 2014, Differential effects of metformin on breast cancer proliferation according to markers of insulin resistance and tumor subtype in a randomized presurgical trial, Breast Cancer Res Treat, 148, 81, 10.1007/s10549-014-3141-1 · DOI
  3. Pollak, 2012, Investigating metformin for cancer prevention and treatment: the end of the beginning, Cancer Discov, 2, 778, 10.1158/2159-8290.CD-12-0263 · DOI
  4. Sadeghi, 2012, Metformin use is associated with better survival of diabetic patients with pancreatic cancer, Clin Cancer Res, 18, 2905, 10.1158/1078-0432.CCR-11-2994 · DOI
  5. Suissa, 2012, Metformin and the risk of cancer: time-related biases in observational studies, Diabetes Care, 35, 2665, 10.2337/dc12-0788 · DOI
  6. Tsilidis, 2014, Metformin does not affect cancer risk: a cohort study in the U.K. Clinical Practice Research Datalink analyzed like an intention-to-treat trial, Diabetes Care, 37, 2522, 10.2337/dc14-0584 · DOI
  7. Andrzejewski, 2014, Metformin directly acts on mitochondria to alter cellular bioenergetics, Cancer Metab, 2, 12, 10.1186/2049-3002-2-12 · DOI
  8. Cusi, 1996, Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus, J Clin Endocrinol Metab, 81, 4059
  9. Fisher, 1996, Insulin promotes pancreatic cancer: evidence for endocrine influence on exocrine pancreatic tumors, J Surg Res, 63, 310, 10.1006/jsre.1996.0266 · DOI
  10. Weinberg, 2015, Targeting mitochondria metabolism for cancer therapy, Nat Chem Biol, 11, 9, 10.1038/nchembio.1712 · DOI
  11. Javeshghani, 2012, Carbon source and myc expression influence the antiproliferative actions of metformin, Cancer Res, 72, 6257, 10.1158/0008-5472.CAN-12-2907 · DOI
  12. Ming, 2014, Dose-dependent AMPK-dependent and independent mechanisms of berberine and metformin inhibition of mTORC1, ERK, DNA synthesis and proliferation in pancreatic cancer cells, PLoS One, 9, e114573, 10.1371/journal.pone.0114573 · DOI
  13. Hochster, 2006, Consensus report of the international society of gastrointestinal oncology on therapeutic progress in advanced pancreatic cancer, Cancer, 107, 676, 10.1002/cncr.22036 · DOI
  14. Lau, 2014, Metformin and erlotinib synergize to inhibit basal breast cancer, Oncotarget, 5, 10503, 10.18632/oncotarget.2391 · DOI
  15. Morgillo, 2013, Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wild-type NSCLC cell lines, Clin Cancer Res, 19, 3508, 10.1158/1078-0432.CCR-12-2777 · DOI
  16. Christensen, 2011, The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c, Pharmacogenet Genomics, 21, 837, 10.1097/FPC.0b013e32834c0010 · DOI
  17. Tempero, 2011, Pancreatic cancer treatment and research: an international expert panel discussion, Ann Oncol, 22, 1500, 10.1093/annonc/mdq545 · DOI
  18. Pollak, 2012, Metformin and pancreatic cancer: a clue requiring investigation, Clin Cancer Res, 18, 2723, 10.1158/1078-0432.CCR-12-0694 · DOI
  19. Nies, 2011, Organic cation transporters (OCTs, MATEs), in vitro and in vivo evidence for the importance in drug therapy, Handb Exp Pharmacol, 201, 105, 10.1007/978-3-642-14541-4_3 · DOI
  20. Yuan, 2013, Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma, Proc Natl Acad Sci USA, 110, 18226, 10.1073/pnas.1317577110 · DOI
  21. Appleyard, 2012, Phenformin as prophylaxis and therapy in breast cancer xenografts, Br J Cancer, 106, 1117, 10.1038/bjc.2012.56 · DOI · Paper page
  22. Pritchard, 2011, Randomized trial of tamoxifen versus combined tamoxifen and octreotide LAR therapy in the adjuvant treatment of early-stage breast cancer in postmenopausal women: NCIC CTG MA.14, J Clin Oncol, 29, 3869, 10.1200/JCO.2010.33.7006 · DOI
  23. Fuchs, 2015, A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial, Ann Oncol, 26, 921, 10.1093/annonc/mdv027 · DOI
  24. Algire, 2011, Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo, Oncogene, 30, 1174, 10.1038/onc.2010.483 · DOI
  25. Maiuri, 2015, Essential role for oxidative phosphorylation in cancer progression, Cell Metab, 21, 11, 10.1016/j.cmet.2014.12.013 · DOI

Cited by

Sorted by citations

See all 361

Metadata

Authors
Kordes, S., Pollak, M. N., Zwinderman, A. H., Mathôt, R. A., Weterman, M. J., Beeker, A., Punt, C. J., Richel, D. J., & Wilmink, J. W.
Venue
The Lancet Oncology
Publisher
Elsevier BV
Published
2015-07
Volume
16
Issue
7
Pages
839-847
ISSN
1470-2045
DOI
10.1016/s1470-2045(15)00027-3
Cited by
361
References
11
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review