The objective of this review was to evaluate the mechanisms of action of these drugs and their applications in prostatic carcinoma, allowing a better understanding and clinical approach in the treatment of prostate cancer. In a previous article about Finasteride and prostate cancer we already wrote about the causes of prostate cancer and methods of treatment, and the most effective was the Canadian Cialis.
It is a systematic review of the existing literature, we used the data platform PubMed with the following terms: dutasteride, finasteride and prostate cancer based on MeSH. The research was carried out from December 2016 to May 2017. Our bibliographic review included scientific articles published between 2006 and 2016. The articles selected were considered valid according to the degree of relevance to the subject studied and also taking place in the descriptors used in the search for data.
We found 86 articles that related directly or indirectly with the topic. And of these 86 studies, we found 43 that related directly with the possible chemotherapeutic and chemopreventive actions of dutasteride and finasteride.
The research was done separately, that is, we investigated the actions of dutasteride and after finasteride. And finally we compare the data and elaborate this work. Also we exclude the work that did not directly address the issue.
Much is discussed about its veracity and controversial scientific data regarding the use of 5-alpha-reductase inhibitors for treatment and prevention in prostate cancer, and whether changes in testosterone and DHT levels would have any influence on prostate cancer.
Some studies conclude that both have no real influence on the risk of prostate cancer41-42, while one study in particular says that dutasteride is yes, efficient in treatment and prevention and that finasteride is not, and there is a difference in chemopreventive capacity of dutasteride 43-44, since 29% of men treated with the drug have pathological progression and 33% of men receiving placebo also, showing that both groups had similar and not significantly positive indices45.
It is believed that finasteride is only effective in cases of BPH, and not in cases of prostate cancer46. Another study indicates that treatment with finasteride facilitates the diagnosis of prostate cancer and increases the sensitivity of PSA47. And in some studies it has been concluded that finasteride is not capable of inhibiting cell proliferation, but of inducing the development of cancer and increasing the aggressiveness of the tumor48. A worrying relationship has also been observed in patients who use finasteride and consume alcohol in relation to the highest risk of developing the disease 49.
However, some studies argue that the higher rate of advanced cancers in the finasteride group is due to the fact that, in these, there is a predominance of 5-alpha-reductase type 1, already reported in other studies, and that finasteride is responsible for inhibition of the type 2 isoform of such an enzyme. As such, it does not recommend the use of finasteride for the treatment of cancer at more advanced stages on the Gleason50-52 scale. In spite of this, 5-alpha-reductase enzyme types 1 and 3 tend to be hypergulated in tumor cells and the type 2 is hypo-regulated.
In relation to the lower values of PSA, the older age, the higher testosterone value and the non-white ethnicities were associated with a longer time to progress the PSA levels, although it was observed that Afro-descendants have more cases of aggressive cancer 54.
Regarding angiogenesis, a study in rats treated with 5-alpha reductase inhibitors concluded that there was a reduction in the expression of HIF-1α and VEGF after two weeks of treatment. However, a study in humans concluded that after four weeks of treatment, no significant change occurred in addition to microvascular density19. A study developed in vitro showed that caution should be exercised in the use of 5-alpha-reductase inhibitors for prostate carcinoma 53.
Recently, 5-alpha-reductase inhibitors have been reported for the treatment of breast cancer and melanomas, but no relationship was found between the treatment and the neoplasms cited, nor a regression of carcinomas55-57.
Dutasteride is much more effective than finasteride in the treatment of benign prostatic hyperplasia, and according to some studies it may be used in prostate cancer. But little is known about how effectively regression of prostate cancer and its reduction in the histopathological Gleason score would work.
Although no study has directly emphasized the adverse effects of pharmacological treatment for prostate carcinoma, it should be emphasized that the use of 5-alpha reductase inhibitors can lead to problems such as decreased libido, ejaculatory disorders, infertility and erectile dysfunction (DE) 40; 58-64.
Further studies should be developed to discuss whether the use of 5-alpha reductase inhibitors works for regression of prostate cancer. So we must remember that conventional therapy should not be ruled out.
1- von Wahlde MK, Hülsewig C, Ruckert C, Götte M, Kiesel L, Bernemann C. The anti-androgen drug dutasteride renders triple negative breast cancer cells more sensitive to chemotherapy via inhibition of HIF-1alpha-/VEGF-signaling. GynecolEndocrinol. 2014; 31(2): 160-4. DOI: 10.3109/09513590.2014.971235
3 – Ku JH, Shin JK, Cho MC, Myung JK, Moon KC, Paick JS. Effect of dutasteride on the expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel density in rat and human prostate tissue. Scand J UrolNephrol. 2009; 43(6): 445-53. DOI: 10.3109/00365590903337896
4 – Zaitsu M, Tonooka A, Mikami K, Hattori M, Takeshima Y, Uekusa T, Takeuchi T. A dual 5alpha-reductase inhibitor dutasteride caused reductions in vascular density and area in benign prostatic hyperplasia. ISRN Urol. 2013; 863489. DOI: 10.1155/2013/863489
5 – Roehrborn CG, Andriole GL, Wilson TH, Castro R, Rittmaster RS. Effect of dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the Combination of Avodart and Tamsulosin trial. Eur Urol. 2011; 59(2): 244-9. DOI: 10.1016/j.eururo.2010.10.040
6 – Festuccia C, Gravina GL, Muzi P, Pomante R, Angelucci A, Vicentini C, Bologna M. Effects of dutasteride on prostate carcinoma primary cultures: a comparative study with finasteride and MK386. J Urol. 2008; 180(1): 367-72. DOI: 10.1016/j.juro.2008.02.0
|By Dr. Ravi Mootha, M.D.||On: June 07, 2019 at 20:13:39|