DOI: 10.25934/pr00007794
title: Co Medication (aspirin, statins and metformin) analysis in patients with metastatic Castration Resistant Prostate Cancer treated with Chemotherapy.

description: Metastatic prostate cancer is usually treated initially with androgen deprivation therapy (ADT).Androgen deprivation therapy is the common treatment for prostate cancer since 1930 that it was first described by Hughins and according to this description he was able to win the Nobel Price. Metastatic prostate cancer are treatment as first line with androgen deprivation therapy that mean to reach a testosterone level lower the 50 ng/dl However, in most patients, the cancer eventually becomes refractory to conventional ADT and the condition ultimately progresses to the metastatic castrate-resistant prostate cancer (mCRPC) stage, for which there is no cure. In 2004, docetaxel was the first drug to show improvement in overall survival in patients suffering from mCRPC and has been widely used in this indication. Major progresses have been achieved since 2010 for the treatment of CRPC. Recent evidence suggests that although prostate cancer becomes castration resistant, cancer cells may remain sensitive to further androgen receptor targeting. Abiraterone acetate, an irreversible steroidal cytochrome P450 (CYP) enzyme 17 (CYP17) inhibitor of both the 17,20-lyase and 17-hydroxylase activities, prolonged overall survival (OS) in patients with mCRPC who had previously received docetaxel.Abiraterona acetate is a drug that interferes in the cholesterol metabolism and decrease the testosterone production inhibiting those enzymes and decreasing the testosterone production at the suprarenal level and intratumorally. The problem that produce that increase adrenocorticotropic hormone (ACTH) because the decrease production of testosterona and secondarly an increase of the mineral corticosteroids. chemotherapy. In addition, abiraterone shows a significant improvement of radiographic progression-free survival (rPFS) and an improved OS in chemotherapy-naïve patients. Therefore, abiraterone has been approved as first line treatment in patients with mCRPC in Europe. However, toxicities attributed to a syndrome of secondary mineralocorticoid excess have been noted with abiraterone and require administration of a glucocorticoid. Enzalutamide, an androgen receptor signaling inhibitor, showed improvement in OS compared with placebo in a randomized phase III trial in patients with mCRPC who had previously received docetaxel chemotherapy and has recently also been shown to significantly prolong OS when given in the pre-chemotherapy setting Enzalutamide was also approved in first line treatment for mCRPC. Three other treatments have also demonstrated OS improvement in mCRPC: a new taxane,like Cabazitaxel that has demostrated activity in those patients progressing to docetaxel and has been incorporated in the armamentarium of the prostate cancer treatment, a bone-targeted alpha-emitter, Radium-223, and an active immunotherapy, Sipuleucel-T. Sipuleucel-T is not available in Europe.
Unfortunately some of these therapies are cross-resistant, thus lowering their cumulative impact on OS. Despite the above-mentioned advances, the median survival of patients with mCRPC is still less than 3 years. Additionally, the costs of the new drugs are very high so that not all countries can afford them and current availability for patients is limited.
The rationale for studying the effect of aspirin, statins and metformin in patients with prostate cancer is due to all these drugs may have a synergistic effect with standard treatments and could prolong radiological progression free survival in patients with mCRPC.
The aim of the study is to retrospectively analyze if concomitant administration of these drugs could improve the disease evolution of our patients treated with chemotherapy.