Home LiteratureArticle Details
PMID: 21415239 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Thiazolidinediones and metformin associated with improved survival of diabetic prostate cancer patients.

Annals of oncology : official journal of the European Society for Medical Oncology ·Vol. 22 ·No. 12 ·2011-12-00 ·Pages 2640-2645

He XX, Tu SM, Lee MH, Yeung SJ

Abstract

The association between antidiabetic medications and the prognosis of human prostate cancer has not been explored. This study examined the impact of these drugs on the outcomes of diabetic patients with prostate cancer to provide a basis for diabetes management strategy in these patients. Records of consecutive prostate cancer patients with coexisting diabetes mellitus type 2 who were treated at the study institution between 15 July 1999 and 31 December 2008 were reviewed. The survival, cancer pathological grade, stage at the time of diagnosis, and antidiabetic pharmacotherapy of the patients were analyzed. A total of 233 consecutive cases were analyzed. In Kaplan-Meier analysis, thiazolidinedione (log-rank, P = 0.005) and metformin (log-rank, P = 0.035) usage were significant predictors of improved overall survival, while insulin and insulin secretagogue usage were not significant predictors. Multivariate Cox regression analysis showed that thiazolidinedione {hazard ratio [HR] = 0.454 [95% confidence interval (CI) 0.213-0.965], P = 0.040} and metformin [HR = 0.550 (95% CI 0.315-0.960), P = 0.035] usage remained as significant predictors of favorable survival after controlling for variables including age, race, Gleason grade, and stage. Thiazolidinediones and metformin appear to be associated with improved overall survival of diabetic prostate cancer patients. The choice of antidiabetic pharmacotherapy may influence overall survival of these patients.

MeSH Terms
Adult Aged Aged, 80 and over Diabetes Mellitus, Type 2/complications,drug therapy,mortality Humans Hypoglycemic Agents/therapeutic use Kaplan-Meier Estimate Male Metformin/therapeutic use Middle Aged Multivariate Analysis Neoplasm Grading Proportional Hazards Models Prostatic Neoplasms/complications,drug therapy,mortality Statistics, Nonparametric Thiazolidinediones/therapeutic use
Chemicals
Hypoglycemic Agents Thiazolidinediones Metformin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
He X-X
Department of Molecular and Cellular Oncology; Emergency Medicine.
Tu S M
Genitourinary Medical Oncology.
Lee M-H
Department of Molecular and Cellular Oncology.
Yeung S-C J
Emergency Medicine; Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: [email protected].
References (53)
53 references, click to expand
  1. AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms.
    Biochem Biophys Res Commun. 2004 Aug 13;321(1):161-7 PMID: 15358229
  2. Thiazolidenediones mediate apoptosis in prostate cancer cells in part through inhibition of Bcl-xL/Bcl-2 functions independently of PPARgamma.
    Cancer Res. 2005 Feb 15;65(4):1561-9 PMID: 15735046
  3. Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy.
    Cancer. 2006 Feb 1;106(3):581-8 PMID: 16388523
  4. Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study.
    Cancer Causes Control. 2009 Nov;20(9):1617-22 PMID: 19653109
  5. Diabetes mellitus and prostate cancer risk among older men: population-based case-control study.
    Br J Cancer. 2004 Jun 1;90(11):2171-5 PMID: 15150583
  6. Analysis of single nucleotide polymorphism C3435T of the multidrug resistance gene MDR1 in acute lymphoblastic leukemia.
    Int J Oncol. 2003 Aug;23(2):509-17 PMID: 12851703
  7. A meta-analysis of diabetes mellitus and the risk of prostate cancer.
    Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2056-62 PMID: 17119028
  8. Marked hyperglycemia after androgen-deprivation therapy for prostate cancer and usefulness of pioglitazone for its treatment.
    Metabolism. 2005 Jan;54(1):55-9 PMID: 15562380
  9. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin.
    Diabetes Care. 2006 Feb;29(2):254-8 PMID: 16443869
  10. Diabetes genes and prostate cancer in the Atherosclerosis Risk in Communities study.
    Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):558-65 PMID: 20142250
  11. History of diabetes mellitus and risk of prostate cancer in physicians.
    Am J Epidemiol. 2004 May 15;159(10):978-82 PMID: 15128610
  12. Targeting AMPK: a new therapeutic opportunity in breast cancer.
    Crit Rev Oncol Hematol. 2008 Jul;67(1):1-7 PMID: 18343152
  13. Insulin sensitivity during combined androgen blockade for prostate cancer.
    J Clin Endocrinol Metab. 2006 Apr;91(4):1305-8 PMID: 16434464
  14. Causes of death in men with prevalent diabetes and newly diagnosed high- versus favorable-risk prostate cancer.
    Int J Radiat Oncol Biol Phys. 2010 Aug 1;77(5):1329-37 PMID: 19879061
  15. Does pre-existing diabetes affect prostate cancer prognosis? A systematic review.
    Prostate Cancer Prostatic Dis. 2010 Mar;13(1):58-64 PMID: 20145631
  16. Diabetes induces stromal remodelling and increase in chondroitin sulphate proteoglycans of the rat ventral prostate.
    Int J Exp Pathol. 2009 Aug;90(4):400-11 PMID: 19659898
  17. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level.
    Oncogene. 2008 Jun 5;27(25):3576-86 PMID: 18212742
  18. Cancer risks in thiazolidinedione users compared to other anti-diabetic agents.
    Pharmacoepidemiol Drug Saf. 2007 May;16(5):485-92 PMID: 17192841
  19. Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults.
    Am J Epidemiol. 2004 Jun 15;159(12):1160-7 PMID: 15191933
  20. Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer.
    Eur J Cancer. 2005 Dec;41(18):2887-95 PMID: 16243513
  21. Diabetes mellitus and risk of prostate cancer: a meta-analysis.
    Diabetologia. 2004 Jun;47(6):1071-8 PMID: 15164171
  22. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer.
    J Natl Cancer Inst. 2010 Jan 6;102(1):39-46 PMID: 19996060
  23. Diabetes mellitus and risk of prostate cancer in the health professionals follow-up study.
    Int J Cancer. 2009 Mar 15;124(6):1398-403 PMID: 19058180
  24. Therapy insight: Influence of type 2 diabetes on the development, treatment and outcomes of cancer.
    Nat Clin Pract Oncol. 2005 Jan;2(1):48-53 PMID: 16264856
  25. HNF1B and JAZF1 genes, diabetes, and prostate cancer risk.
    Prostate. 2010 May 1;70(6):601-7 PMID: 19998368
  26. Association of diabetes with prostate cancer risk in the multiethnic cohort.
    Am J Epidemiol. 2009 Apr 15;169(8):937-45 PMID: 19240222
  27. Diabetes mellitus and risk of prostate cancer (United States).
    Cancer Causes Control. 1998 Jan;9(1):3-9 PMID: 9486458
  28. Antidiabetic therapies affect risk of pancreatic cancer.
    Gastroenterology. 2009 Aug;137(2):482-8 PMID: 19375425
  29. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes.
    Nat Genet. 2007 Aug;39(8):977-83 PMID: 17603485
  30. The critical role of the bone microenvironment in cancer metastases.
    Mol Cell Endocrinol. 2009 Oct 30;310(1-2):71-81 PMID: 19616059
  31. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells.
    Cancer Res. 2006 Nov 1;66(21):10269-73 PMID: 17062558
  32. The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth.
    J Cell Mol Med. 2011 Apr;15(4):825-36 PMID: 20455996
  33. Regulatory action on rosiglitazone by the U.S. Food and Drug Administration.
    N Engl J Med. 2010 Oct 14;363(16):1489-91 PMID: 20942663
  34. Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes.
    J Clin Oncol. 2007 Apr 20;25(12):1476-81 PMID: 17442990
  35. PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells.
    Oncogene. 2004 Jan 22;23(3):786-94 PMID: 14737113
  36. Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer.
    Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10990-5 PMID: 10984506
  37. Diabetes mellitus and the risk of prostate cancer.
    Cancer Invest. 2002;20(2):157-65 PMID: 11901534
  38. Thiazolidinediones as anti-cancer agents.
    Cancer Ther. 2008;6(A):25-34 PMID: 19079765
  39. Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy.
    Cancer. 2004 Oct 1;101(7):1569-74 PMID: 15468186
  40. Postload plasma glucose concentration and 27-year prostate cancer mortality (United States).
    Cancer Causes Control. 2001 Oct;12(8):763-72 PMID: 11562117
  41. Prospective study of colorectal cancer risk and physical activity, diabetes, blood glucose and BMI: exploring the hyperinsulinaemia hypothesis.
    Br J Cancer. 2001 Feb 2;84(3):417-22 PMID: 11161410
  42. The potential of antidiabetic thiazolidinediones for anticancer therapy.
    Expert Opin Investig Drugs. 2006 Sep;15(9):1039-49 PMID: 16916271
  43. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission.
    Cancer Res. 2009 Oct 1;69(19):7507-11 PMID: 19752085
  44. PPARgamma-independent antitumor effects of thiazolidinediones.
    Cancer Lett. 2009 Apr 18;276(2):119-24 PMID: 18790559
  45. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes.
    Diabetologia. 2009 Sep;52(9):1766-77 PMID: 19572116
  46. Diabetes and the risk of prostate cancer: the role of diabetes treatment and complications.
    Prostate Cancer Prostatic Dis. 2007;10(1):46-51 PMID: 17033617
  47. Mortality from site-specific malignancies in type 2 diabetic patients from Verona.
    Diabetes Care. 2003 Apr;26(4):1047-51 PMID: 12663571
  48. Antidiabetic medication and prostate cancer risk: a population-based case-control study.
    Am J Epidemiol. 2008 Oct 15;168(8):925-31 PMID: 18700234
  49. Wnt and PPARgamma signaling in osteoblastogenesis and adipogenesis.
    Nat Rev Rheumatol. 2009 Aug;5(8):442-7 PMID: 19581903
  50. Diabetes and risk of prostate cancer in a prospective cohort of US men.
    Am J Epidemiol. 2005 Jan 15;161(2):147-52 PMID: 15632264
  51. Prostate cancer risk among men with diabetes mellitus (Spain).
    Cancer Causes Control. 2005 Nov;16(9):1055-8 PMID: 16184470
  52. Black race is an adverse prognostic factor for prostate cancer recurrence following radical prostatectomy in an equal access health care setting.
    J Urol. 1996 May;155(5):1667-73 PMID: 8627850
  53. Genetic susceptibility to type 2 diabetes is associated with reduced prostate cancer risk.
    Hum Hered. 2010;69(3):193-201 PMID: 20203524
Article Info
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
Abbr.
Ann Oncol
ISSN
1569-8041
DOI
10.1093/annonc/mdr020
Email
[email protected]
Published
2011-12-00
Epub
2011-00-17
Pages
2640-2645
Language
English
Region
England
NLM ID
9007735
PMCID
PMC3221513
Subset
IM
Grants
NCI NIH HHS · R01 CA089266 · United States
NCI NIH HHS · R56 CA089266 · United States
NCI NIH HHS · CA16672 · United States
NCI NIH HHS · R01CA 089266 · United States
External Links
PubMed source DOI: 10.1093/annonc/mdr020 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2