pioglitazone and Cancer of Prostate studies

Pioglitazone: A thiazolidinedione and PPAR GAMMA agonist that is used in the treatment of TYPE 2 DIABETES MELLITUS.
pioglitazone : A member of the class of thiazolidenediones that is 1,3-thiazolidine-2,4-dione substituted by a benzyl group at position 5 which in turn is substituted by a 2-(5-ethylpyridin-2-yl)ethoxy group at position 4 of the phenyl ring. It exhibits hypoglycemic activity.

Research Excerpts

Excerpt	Relevance	Reference
"Among 193,099 persons in the bladder cancer cohort, 34,181 (18%) received pioglitazone (median duration, 2."	7.81	Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes. ( Bilker, W; Ehrlich, SF; Ferrara, A; Habel, LA; Hedderson, MM; Lewis, JD; Mamtani, R; Nessel, L; Peng, T; Quesenberry, CP; Strom, BL; Van Den Eeden, SK; Vaughn, DJ, 2015)
"Here we demonstrate 2 patients who showed marked hyperglycemia after androgen-deprivation therapy for prostate cancer and the efficacy of the thiazolidinedione pioglitazone on their glycemic control."	7.73	Marked hyperglycemia after androgen-deprivation therapy for prostate cancer and usefulness of pioglitazone for its treatment. ( Azuma, J; Inaba, M; Kasayama, S; Kawase, I; Koga, M; Nishimura, K; Okuyama, A; Otani, Y; Takaha, N, 2005)
"In LNCaP, a human androgen-dependent prostate cancer cell line, PGZ also inhibited cyclin D1 expression and the activation of both p38 MAPK and NFκB."	5.43	Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis. ( Kato, H; Kobayashi, M; Kuno, T; Mori, Y; Nagano, A; Nagayasu, Y; Naiki-Ito, A; Suzuki, S; Takahashi, S, 2016)
"Among 193,099 persons in the bladder cancer cohort, 34,181 (18%) received pioglitazone (median duration, 2."	3.81	Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes. ( Bilker, W; Ehrlich, SF; Ferrara, A; Habel, LA; Hedderson, MM; Lewis, JD; Mamtani, R; Nessel, L; Peng, T; Quesenberry, CP; Strom, BL; Van Den Eeden, SK; Vaughn, DJ, 2015)
"Here we demonstrate 2 patients who showed marked hyperglycemia after androgen-deprivation therapy for prostate cancer and the efficacy of the thiazolidinedione pioglitazone on their glycemic control."	3.73	Marked hyperglycemia after androgen-deprivation therapy for prostate cancer and usefulness of pioglitazone for its treatment. ( Azuma, J; Inaba, M; Kasayama, S; Kawase, I; Koga, M; Nishimura, K; Okuyama, A; Otani, Y; Takaha, N, 2005)
"Trends of decreased bladder cancer and increased prostate cancer were observed in the pioglitazone group during follow-up; however, these imbalances should be interpreted with caution because of the limitations of the observational study design."	2.82	Ten-year observational follow-up of PROactive: a randomized cardiovascular outcomes trial evaluating pioglitazone in type 2 diabetes. ( Erdmann, E; Harding, S; Lam, H; Perez, A, 2016)
"Nonalcoholic fatty liver disease (NAFLD), the most prevalent cause of chronic liver disease worldwide, is strongly associated with obesity and insulin resistance."	2.61	Nonalcoholic Fatty Liver Disease and Obesity Treatment. ( Brunner, KT; Henneberg, CJ; Long, MT; Wilechansky, RM, 2019)
"Cases were 3513 patients with prostate cancer aged over 40 years, and the controls were 3513 patients without prostate cancer, matched with prostate cancer cases on age, and having a medical care utilization episode in the year of the index prostate cancer (1 control per case)."	1.51	Association Between Pioglitazone Use and Prostate Cancer: A Population-Based Case-Control Study in the Han Population. ( Huang, CY; Kao, LT; Lin, HC; Xirasagar, S, 2019)
"Pioglitazone is a widely used anti-diabetic drug that induces cytotoxicity in cancer cells; however, its clinical use is questioned due to its associated liver toxicity caused by increased oxidative stress."	1.43	Redox nanoparticle increases the chemotherapeutic efficiency of pioglitazone and suppresses its toxic side effects. ( Nagasaki, Y; Sakharkar, MK; Thangavel, S; Yoshitomi, T, 2016)
"In LNCaP, a human androgen-dependent prostate cancer cell line, PGZ also inhibited cyclin D1 expression and the activation of both p38 MAPK and NFκB."	1.43	Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis. ( Kato, H; Kobayashi, M; Kuno, T; Mori, Y; Nagano, A; Nagayasu, Y; Naiki-Ito, A; Suzuki, S; Takahashi, S, 2016)
"Pioglitazone is an anti-diabetic agent with recognized antifibrotic and vasculoprotective properties, which can protect smooth muscle function."	1.40	Pioglitazone prevents cavernosal nerve injury after radical prostatectomy. ( Aliperti, LA; Hellstrom, WJ, 2014)
"However, PC3, an androgen-insensitive prostate cancer cell line with deletion of p53 showed an appreciable post-transcriptional induction of p21 expression after treatment with pioglitazone."	1.33	The PPAR-gamma agonist pioglitazone post-transcriptionally induces p21 in PC3 prostate cancer but not in other cell lines. ( Gartel, AL; Radhakrishnan, SK, 2005)
"Using cells and prostate cancer xenograft mouse models, we demonstrate in this study that a combination treatment using the PPARgamma agonist pioglitazone and the histone deacetylase inhibitor valproic acid is more efficient at inhibiting prostate tumor growth than each individual therapy."	1.33	Peroxisome proliferator-activated receptor gamma regulates E-cadherin expression and inhibits growth and invasion of prostate cancer. ( Abella, A; Annicotte, JS; Berthe, ML; Culine, S; Dubus, P; Fajas, L; Fritz, V; Iankova, I; Iborra, F; Maudelonde, T; Miard, S; Noël, D; Pillon, A; Sarruf, D, 2006)

Research

Studies (16)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

Incident Diagnosis of Bladder Cancer (10-year Analysis)

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	5 (31.25)	29.6817
2010's	11 (68.75)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Metwally, K	1
Pratsinis, H	1
Kletsas, D	1
Kao, LT	1
Xirasagar, S	1
Lin, HC	1
Huang, CY	1
Brunner, KT	1
Henneberg, CJ	1
Wilechansky, RM	1
Long, MT	1
Gomella, LG	1
Aliperti, LA	1
Hellstrom, WJ	1
Lewis, JD	1
Habel, LA	1
Quesenberry, CP	1
Strom, BL	1
Peng, T	1
Hedderson, MM	1
Ehrlich, SF	1
Mamtani, R	1
Bilker, W	1
Vaughn, DJ	1
Nessel, L	1
Van Den Eeden, SK	1
Ferrara, A	1
Erdmann, E	1
Harding, S	1
Lam, H	1
Perez, A	1
Thangavel, S	1
Yoshitomi, T	1
Sakharkar, MK	1
Nagasaki, Y	1
Suzuki, S	1
Mori, Y	1
Nagano, A	1
Naiki-Ito, A	1
Kato, H	1
Nagayasu, Y	1
Kobayashi, M	1
Kuno, T	1
Takahashi, S	1
Gottfried, E	1
Rogenhofer, S	2
Waibel, H	1
Kunz-Schughart, LA	1
Reichle, A	3
Wehrstein, M	1
Peuker, A	1
Peter, K	1
Hartmannsgruber, G	1
Andreesen, R	2
Kreutz, M	1
Walter, B	1
Vogelhuber, M	1
Berand, A	1
Wieland, WF	1
Inaba, M	1
Otani, Y	1
Nishimura, K	1
Takaha, N	1
Okuyama, A	1
Koga, M	1
Azuma, J	1
Kawase, I	1
Kasayama, S	1
Radhakrishnan, SK	1
Gartel, AL	1
Yang, CC	1
Ku, CY	1
Wei, S	1
Shiau, CW	1
Chen, CS	2
Pinzone, JJ	1
Ringel, MD	1
Vogt, T	1
Coras, B	1
Hafner, C	1
Landthaler, M	1
Annicotte, JS	1
Iankova, I	1
Miard, S	1
Fritz, V	1
Sarruf, D	1
Abella, A	1
Berthe, ML	1
Noël, D	1
Pillon, A	1
Iborra, F	1
Dubus, P	1
Maudelonde, T	1
Culine, S	1
Fajas, L	1

Trial	Enrollment	Study Type	Start Date	Status
Calisthenics Versus High-intensity Interval Exercises on Health-related Outcomes in Patients With Non-alcoholic Fatty Liver[NCT06032650]	60 participants (Anticipated)	Interventional	2023-10-31	Not yet recruiting
Cohort Study of Pioglitazone and Bladder Cancer in Patients With Diabetes[NCT01637935]	193,099 participants (Actual)	Observational	2004-07-31	Completed
An Observational Study of Patient Cohorts Who Previously Received Long-term Treatment With Pioglitazone or Placebo in Addition to Existing Antidiabetic Medications.[NCT02678676]	3,599 participants (Actual)	Observational [Patient Registry]	2004-11-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Incident bladder cancers were identified from January 1, 1997 to December 31, 2012. (NCT01637935)
Timeframe: January 1, 1997 to December 31, 2012

Incident Diagnosis of Bladder Cancer by Cumulative Dose of Pioglitazone (10 Year Analysis)

Incident Diagnosis of Bladder Cancer by Duration of Pioglitazone Therapy (10 Year Analysis)

Incident Diagnosis of Bladder Cancer by Time Since Starting Pioglitazone (10 Year Analysis)

Stage of Bladder Cancer (10 Year Analysis)

Incidences With Malignancies

Intervention	events per 100,000 person years (Number)
Pioglitazone Exposed Group	89.8
Pioglitazone Unexposed Group	75.9

Intervention	events per 100,000 person years (Number)
	1 - 14000 mg	14001 - 40000 mg	>40000 mg
Pioglitazone Exposed Group	69.1	96.9	101.4
Pioglitazone Unexposed Group	NA	NA	NA

Intervention	events per 100,000 person years (Number)
	Less than 1.5 years	1.5 - 4.0 years	More than 4 years
Pioglitazone Exposed Group	67.5	88.4	113.7
Pioglitazone Unexposed Group	NA	NA	NA

Intervention	events per 100,000 person years (Number)
	Less than 4.5 years	4.5 -8.5 years	More than 8.0 years
Pioglitazone Exposed Group	68.2	111.6	125.8
Pioglitazone Unexposed Group	NA	NA	NA

Intervention	percentage of participants (Number)
	PUNLMP	In situ	Local	Regional	Distant	Undetermined
Pioglitazone Exposed Group	1	50	40	4	2	3
Pioglitazone Unexposed Group	1	49	38	6	3	3

Percentage of participants with incidences of at least 1 malignancy was reported. All malignancies included adrenal, biliary, bladder, brain, breast, cervix, colon/rectal, gastric, hematological, hepatic, lung, mesothelioma, metastases, oesophageal, oropharyngeal, ovarian/uterine, pancreas, prostate, renal, skin and others. (NCT02678676)
Timeframe: Up to Year 10

Percentage of Participants With First Occurrence of Macro-vascular Event or Death

Intervention	percentage of participants (Number)
Pioglitazone	12.9
Placebo	13.2

The composite macro-vascular event or death included all-cause mortality, non-fatal myocardial infarction, cardiac intervention, stroke, major leg amputation (above the ankle), bypass surgery or revascularization in the leg. The percentage of participants in the observational study population having first occurrence of macro-vascular event or death during the 10-year observational study period was analyzed. The data were analyzed using the Cox regression with respect to time to the first occurrence of macro-vascular event or death. (NCT02678676)
Timeframe: Up to Year 10

Article	Year
Novel 2,4- thiazolidinediones: Synthesis, in vitro cytotoxic activity, and mechanistic investigation. European journal of medicinal chemistry, 2017, Jun-16, Volume: 133 Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Survival; Fem	2017
Association Between Pioglitazone Use and Prostate Cancer: A Population-Based Case-Control Study in the Han Population. Journal of clinical pharmacology, 2019, Volume: 59, Issue:3 Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Comorbidity; Diabetes Mellitus, Type 2; Humans	2019
Actos, slings, finasteride, and the vaccine compensation solution. The Canadian journal of urology, 2013, Volume: 20, Issue:2 Topics: Finasteride; Humans; Liability, Legal; Male; Patient Rights; Pioglitazone; Prostatic Neoplasms; Risk	2013
Pioglitazone prevents cavernosal nerve injury after radical prostatectomy. Medical hypotheses, 2014, Volume: 82, Issue:4 Topics: Erectile Dysfunction; Fibrosis; Humans; Male; Models, Theoretical; Muscle, Smooth; Penis; Pioglitazo	2014
Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes. JAMA, 2015, Jul-21, Volume: 314, Issue:3 Topics: Adult; Aged, 80 and over; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Female; H	2015
Redox nanoparticle increases the chemotherapeutic efficiency of pioglitazone and suppresses its toxic side effects. Biomaterials, 2016, Volume: 99 Topics: Administration, Oral; Animals; Antineoplastic Agents; Apoptosis; Biocompatible Materials; Cell Line,	2016
Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis. International journal of molecular sciences, 2016, Dec-10, Volume: 17, Issue:12 Topics: Adenocarcinoma; Animals; Body Weight; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Disease	2016
Pioglitazone modulates tumor cell metabolism and proliferation in multicellular tumor spheroids. Cancer chemotherapy and pharmacology, 2011, Volume: 67, Issue:1 Topics: Cell Line, Tumor; Cell Proliferation; Chromans; Deoxyglucose; Humans; Hydrogen-Ion Concentration; Hy	2011
Marked hyperglycemia after androgen-deprivation therapy for prostate cancer and usefulness of pioglitazone for its treatment. Metabolism: clinical and experimental, 2005, Volume: 54, Issue:1 Topics: Aged; Aged, 80 and over; Androgen Receptor Antagonists; Glycated Hemoglobin; Humans; Hyperglycemia;	2005
The PPAR-gamma agonist pioglitazone post-transcriptionally induces p21 in PC3 prostate cancer but not in other cell lines. Cell cycle (Georgetown, Tex.), 2005, Volume: 4, Issue:4 Topics: Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p21; Gene Expression Regulation, Neoplastic; Hum	2005
Peroxisome proliferator-activated receptor gamma-independent repression of prostate-specific antigen expression by thiazolidinediones in prostate cancer cells. Molecular pharmacology, 2006, Volume: 69, Issue:5 Topics: Animals; Cell Line, Tumor; Dihydrotestosterone; Humans; Male; Pioglitazone; PPAR gamma; Prostate-Spe	2006
Antiangiogenic therapy in metastatic prostate carcinoma complicated by cutaneous lupus erythematodes. The Lancet. Oncology, 2006, Volume: 7, Issue:8 Topics: Angiogenesis Inhibitors; Antimetabolites, Antineoplastic; Antineoplastic Agents, Alkylating; Capecit	2006
Peroxisome proliferator-activated receptor gamma regulates E-cadherin expression and inhibits growth and invasion of prostate cancer. Molecular and cellular biology, 2006, Volume: 26, Issue:20 Topics: Animals; Cadherins; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Disease Progressio	2006

pioglitazone and Cancer of Prostate