Pharmacotherapy for prostate cancer, with emphasis on hormonal treatments

Abstract

For more than half a century, hormonal therapy has been one of the cornerstones of prostate cancer therapy. However, the position and timing of androgen deprivation therapy is continuously challenged. Nowadays, it is often combined with other types of treatment in a multi-modal approach, especially with radiation therapy. Besides the well-known luteinising hormone-releasing hormone agonists, several developments have been introduced (e.g., luteinising hormone-releasing hormone antagonists or improved depot formulations achieving a better pharmacokinetic slope and lower testosterone levels). Research developments include a better understanding of the different gonadotropin-releasing hormone isoforms, the ligand-independent transformation of the androgen receptor and androgen receptor overexpression in hormone-insensitive disease. Prostate cancer, previously thought to be chemotherapy insensitive, is now treated at the metastatic stage by taxane-based chemotherapies. The combination of hormonal therapy and chemotherapy is currently studied at various stages of the disease, as early as localised or locally advanced prostate cancer. It is very likely that, in the future, pharmacological treatment for prostate cancer will include combination therapies rather than monotherapies. The authors suggest an in-depth re-evaluation of the place of androgen deprivation therapy in prostate cancer.

Hormonal therapy in metastatic prostate cancer: current perspectives and controversies

“…iii) skeletal metastases with severe bone pain not responding to narcotic analgesia use. 31 At present, GnRH agonists are the mainstay of treatment for advanced prostate cancer according to the European Association of Urology (EAU) guidelines. 21 Recently, GnRH antagonists have emerged as new effective androgen ablation agents.…”

Current Medical and Surgical Options for Androgen Deprivation in Prostate Cancer Patients

“…The theoretical advantages of GnRH antagonists compared with agonists include: i) no flare reactions; ii) rapid down regulation of GnRH membrane receptors; iii) no need for combination therapy with an antiandrogen, resulting in improved compliance and fewer side effects; iv) more targeted therapy, including direct action on the primary and secondary tumor cells; v) reduced costs; and vi) more pronounced down regulation of testosterone [30]. GnRH antagonists are indicated for palliative treatment of men with advanced symptomatic prostate cancer, in whom GnRH-A therapy alone is not appropriate because of an initial increase in testosterone, who refuse surgical castration, and who have one or more of the following: (1) risk of neurological compromise due to metastases; (2) ureteral or bladder outlet obstruction due to local encroachment or metastatic disease; or (3) severe bone pain from skeletal metastases persisting with narcotic analgesia use [30].…”

“…The cumulative risk increases with the duration of treatment. Several third and fourth-generation GnRH antagonists have been developed with fewer side effects and are currently under clinical investigations (abarelix, acyline, teverelix, getrorelix, degarelix, ganirelix, iturelix, orntide) [30].…”