Abstract
Background
The current study aims to provide an assessment of the impact of diabetes mellitus
and its metformin treatment on the outcomes of castration-resistant prostate cancer
(CRPC) within a pooled dataset of 3 clinical trials.
Materials and Methods
This is a pooled analysis of the comparator arms of 3 clinical trials (NCT00988208; NCT00273338; NCT00519285) that evaluated docetaxel/prednisone in chemotherapy-naive patients with CRPC. Overall
survival according to patient subsets (nondiabetic patients, diabetic metformin patients,
and diabetic non-metformin patients) was assessed using Kaplan-Meier analysis and
log-rank testing. Multivariate analysis of factors affecting overall survival was
then performed through Cox regression analysis.
Results
A total of 1600 patients were enrolled into the current study, of which 147 patients
were diabetic patients receiving metformin, 116 patients were diabetic patients not
receiving metformin, and 1337 were nondiabetic patients. Using Kaplan-Meier analysis,
no evidence for overall survival difference was found among the 3 patient subsets
(diabetic metformin patients, diabetic non-metformin patients, and nondiabetic patients)
(P = .908). The following factors were predictive of worse overall survival in multivariate
analysis: lower hemoglobin (P < .0001), lower body mass index (P = .041), shorter docetaxel treatment (P < .0001), and higher M1 sub-stage (P = .016).
Conclusion
Diabetes mellitus (with or without metformin treatment) does not seem to have a significant
effect on the outcomes of chemotherapy-naive patients with CRPC treated with docetaxel/prednisone.
Further studies are needed to clarify the impact of metabolic syndrome on the outcomes
of androgen-dependent prostate cancer.
Keywords
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References
World Health Organization; International Agency for Research on Cancer. Global Cancer Observatory. Available at: globocan.iarc.fr. Accessed: November 27, 2016.
- Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2015; 26: v69-v77
- Metabolic coupling and the reverse Warburg effect in cancer: implications for novel biomarker and anticancer agent development.Semin Oncol. 2017; 44: 198-203
- Diabetes and cancer: a consensus report.Diabetes Care. 2010; 33: 1674-1685
- Metabolic syndrome predicts prostate cancer in a cohort of middle-aged Norwegian men followed for 27 years.Am J Epidemiol. 2006; 164: 769-774
- Hyperglycemia and prostate cancer recurrence in men treated for localized prostate cancer.Prostate Cancer Prostatic Dis. 2013; 16: 204-208
- Diabetes and outcomes after radical prostatectomy: are results affected by obesity and race? Results from the shared equal-access regional cancer hospital database.Cancer Epidemiol Biomarkers Prev. 2010; 19: 9-17
- The association of diabetes and obesity with prostate cancer progression: HCaP-NC.Prostate. 2017; 77: 878-887
- Metformin in cancer prevention and therapy.Ann Transl Med. 2014; 2: 57
- Recent advances in the use of metformin: can treating diabetes prevent breast cancer?.Biomed Res Int. 2015; 2015: 548436
- Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth.Cancer Res. 2007; 67: 6745-6752
- The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells.Cell Cycle. 2009; 8: 88-96
- Adiposity and diabetes in breast and prostate cancer.in: Kolonin M.G. Adipose Tissue and Cancer. Springer New York, New York2013: 33-51
- Impact of diabetes, insulin, and metformin use on the outcome of patients with human epidermal growth factor receptor 2-positive primary breast cancer: analysis from the ALTTO phase III randomized trial.J Clin Oncol. 2017; 35: 1421-1429
- Metformin and reduced risk of cancer in diabetic patients.BMJ. 2005; 330: 1304-1305
- Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin.Diabetes Care. 2006; 29: 254-258
- Does pre-existing diabetes affect prostate cancer prognosis? A systematic review.Prostate Cancer Prostatic Dis. 2010; 13: 58-64
- Project Data Sphere.(Available at:)https://www.projectdatasphere.org/projectdatasphere/html/homeDate accessed: October 7, 2017
- Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial.Lancet Oncol. 2013; 14: 760-768
- Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer.J Clin Oncol. 2011; 29: 2191-2198
- Docetaxel and prednisone with or without lenalidomide in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (MAINSAIL): a randomised, double-blind, placebo-controlled phase 3 trial.Lancet Oncol. 2015; 16: 417-425
- Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer.J Clin Oncol. 2014; 32: 671-677
- Prostascore: a simplified tool for predicting outcomes among patients with treatment-naive advanced prostate cancer.Clin Oncol (R Coll Radiol). 2017; 29: 732-738
- MP57-14: The association of BMI and DM with survival among patients with metastatic or castration-resistant prostate cancer.J Urol. 2017; 197: e769
- Concurrent diabetes mellitus may negatively influence clinical progression and response to androgen deprivation therapy in patients with advanced prostate cancer.Front Oncol. 2015; 5: 129
- The interactions between insulin and androgens in progression to castrate-resistant prostate cancer.Adv Urol. 2012; 2012: 248607
- Prognostic value of body mass index in Korean patients with castration-resistant prostate cancer.Korean J Urol. 2012; 53: 761-765
- Sarcopenia is a poor prognostic factor of castration-resistant prostate cancer treated with docetaxel therapy.Prostate Int. 2018;
- Patient characteristics and overall survival in patients with post-docetaxel metastatic castration-resistant prostate cancer in the community setting.Med Oncol. 2017; 34: 160
- Association of survival benefit with docetaxel in prostate cancer and total number of cycles administered: a post hoc analysis of the MAINSAIL study.JAMA Oncol. 2017; 3: 68-75
- Influence of concurrent medications on outcomes of men with prostate cancer included in the TAX 327 study.Can Urol Assoc J. 2013; 7: E74-E81
- Assessment of a prognostic model, PSA metrics and toxicities in metastatic castrate resistant prostate cancer using data from Project Data Sphere (PDS).PLoS One. 2017; 12: e0170544
Article info
Publication history
Published online: September 26, 2018
Accepted:
September 21,
2018
Received in revised form:
September 17,
2018
Received:
August 22,
2018
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.