Investigational luteinizing hormone releasing hormone (LHRH) agonists and other hormonal agents in early stage clinical trials for prostate cancer

ABSTRACT

Introduction: The treatment and management of prostate cancer continues to evolve; newer classes of agents and combination therapies are being developed and some are being investigated in early phase clinical trials.

Areas covered: We discuss investigational hormonal agents for the treatment of prostate cancer and focus primarily on luteinizing hormone releasing hormone (LHRH) agonists in early stage trials. We look at agents that target the hormonal axis, including anti-androgens, gonadotropins, estrogenic agents and progestogenic agents and other non-hormonal agents often used in combination with LHRH agonists. We review these candidates in the specific clinical niche in which they might find utility.

Expert opinion: Of all candidate compounds being evaluated in clinical trials, very few will receive FDA approval. Few, if any of the investigational agents discussed here will be used routinely in clinical practice for treating prostate cancer. Recognizing the reasons for the failure of agents to advance to later stage trials is important. Furthermore, a thorough understanding of the mechanisms underlying prostate cancer pathogenesis, including various points in the HGPA and parallel pathways, will help identify potentially actionable targets.

KEYWORDS:

• Prostate cancer
• hormonal therapy
• investigational
• luteinizing hormone releasing hormone agonist

Article Highlights

• The management of advanced prostate cancer continues to evolve, with newer classes of agents or combination therapies being developed.

• LHRH agonism has been the most common approach to androgen ablation, though other hormonal targets have also been of interest, including androgen synthesis, the androgen receptor, GnRH antagonism, estrogen receptors, and progesterone receptors.

• Zoptarelin doxorubicin is the newest investigational LHRH agonist showing promise.

• Very few drugs in early clinical phase trials ultimately make it through the drug development pipeline to FDA approval.

• Combinatorial approaches involving androgen deprivation augmented with targeted therapies of other pathways, are under active investigation.

• Personalized medicine will likely play an increasing role in the future development of prostate cancer therapies.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.