Repurposing Metformin as Anticancer Drug: in Advanced Prostate Cancer

This study evaluate the addition of metformin to standard of care in locally advanced and metastatic prostate cancer, half the patient will receive metformin in combination with standard treatment, and the other half will receive the standard of care only

Sex

Male

Minimum age

18 Years

Inclusion Criteria:

1. High-risk newly diagnosed non-metastatic node-negative disease at least two of:

   * Stage T3/4, PSA≥40ng/ml or Gleason sum score 8-10
   * Intention to treat with radical radiotherapy (unless there is a contraindication)
2. OR newly diagnosed metastatic or node-positive disease at least one of:

   * Stage T any N+ M0
   * Stage T any Nany M+
3. OR previously treated with radical surgery and/or radiotherapy, now relapsing

   At least one of:

   (-PSA ≥4ng/ml and rising with doubling time less than 6 months,N+, M+)
4. And for all patients

   * Age \> 18 years
   * Histologically confirmed prostate adenocarcinoma
   * Intention to treat with long-term androgen deprivation therapy
   * Fit for all protocol treatment and follow-up, ECOG performance status 0-2
   * Diabetic and non-diabetic patients
   * Patients with adequate organ function(AST - ALAT ≤ 2.5x ULN,Bilirubin ≤ 1.5 x ULN)

Exclusion Criteria:

1. Age \< 18 years
2. Excessive alcohol intake, acute or chronic
3. Patients already treated with Metformin or an analoge
4. Known hypersensitivity or allergy to Metformin or any of the excipients.
5. Patients with a history of lactic acidosis
6. Patient treated for a cancer other than prostate cancer, with the exception of basal cell carcinoma
7. Acute or chronic metabolic acidosis.
8. Patients suffering from severe dehydration.
9. Patients with chronic heart failure.
10. Patients with hepatic impairment.
11. Patients with severe renal disease.

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• RESULTDowling RJ, Goodwin PJ, Stambolic V. Understanding the benefit of metformin use in cancer treatment. BMC Med. 2011 Apr 6;9:33. doi: 10.1186/1741-7015-9-33. PMID 21470407
• RESULTEriksson A, Attvall S, Bonnier M, Eriksson JW, Rosander B, Karlsson FA. Short-term effects of metformin in type 2 diabetes. Diabetes Obes Metab. 2007 Jul;9(4):483-9. doi: 10.1111/j.1463-1326.2006.00624.x. PMID 17587390
• RESULTHamilton RJ. Metformin for castrate-resistant prostate cancer: learning more about an old dog's new tricks. Eur Urol. 2014 Sep;66(3):475-7; discussion 477-8. doi: 10.1016/j.eururo.2014.01.013. Epub 2014 Jan 23. No abstract available. PMID 24472709
• RESULTHankinson SJ, Fam M, Patel NN. A review for clinicians: Prostate cancer and the antineoplastic properties of metformin. Urol Oncol. 2017 Jan;35(1):21-29. doi: 10.1016/j.urolonc.2016.10.009. Epub 2016 Nov 9. PMID 27836248
• RESULTMayer MJ, Klotz LH, Venkateswaran V. Metformin and prostate cancer stem cells: a novel therapeutic target. Prostate Cancer Prostatic Dis. 2015 Dec;18(4):303-9. doi: 10.1038/pcan.2015.35. Epub 2015 Jul 28. PMID 26215782
• RESULTRanasinghe WK, Sengupta S, Williams S, Chang M, Shulkes A, Bolton DM, Baldwin G, Patel O. The effects of nonspecific HIF1alpha inhibitors on development of castrate resistance and metastases in prostate cancer. Cancer Med. 2014 Apr;3(2):245-51. doi: 10.1002/cam4.189. Epub 2014 Jan 27. PMID 24464861