Prostate Cancer Drugs Currently Approved or in Late-stage Clinical Trials.

Day’s end in the Gulf of Mexico at Boca Grande, Florida; BJ Gabrielsen

At the time of this writing, there are thirteen (14) drugs currently approved by the Food and Drug Administration for the treatment of prostate cancer. There are others which are in various stages of clinical development or review.  A number of these have been mentioned in earlier blog posts on this website. The National Cancer Institute (NCI) of the National Institutes of Health (NIH) has an excellent website (see also http://www.cancer.gov/cancertopics/types/prostate). A list of approved drugs is also given. Personally, I am finding it helpful to briefly list the drugs discussed in this website with a description of their potential uses and current developmental status. It is my intent to maintain this website listing as current as possible with new additions and developmental updates.

Therapeutic agents already approved by the FDA include:

1 – Lupron (Leuprolide Acetate); used to suppress the production of testosterone in androgen deprivation or hormonal therapy. Leuprolide falls into a class of drugs called luteinizing hormone-releasing hormone (LHRH) agonists. Others drugs in this class include goserelin (Zoladex), triptorelin (Trelstar) and histrelin (Vantas).

2 – Prednisone; used in conjunction with chemotherapy to reduce its potential side effects, inflammation and suppress the body’s immune response.

3 – Taxotere (Docetaxel); a second generation, synthetic taxane drug based upon compounds (Taxol) derived from the European yew tree and used as a potent and broad chemotherapeutic agent. In treating metastatic, hormone-refractory (resistant) prostate cancer, it may be used used in conjunction with other anti-cancer agents and prednisone. Taxotere may be combined with Carboplatin, Xeloda (see below) or Emcyt. It has also been used effectively combined with Avastin and Revlimid.

4 – Jevtana (Cabazitaxel); a new taxane (see taxotere) administered with prednisone and used to treat metastatic, hormone-refractory (resistant) prostate cancer in men who have already undergone chemotherapy. It was approved by the FDA in spring, 2010 for use in metastatic, hormone-resistant prostate cancer patients who have failed chemotherapy with docetaxel (taxotere). (Discussed in the May 7th, 2011 blog post and see http://www.cancer.gov/clinicaltrials/results/cabazitaxel0310).

5 – Zytiga (Abiraterone acetate); This once-daily, oral drug from Johnson & Johnson was approved in April, 2011 for use in men with metastatic, hormone-refractory prostate cancer who have failed docetaxel (taxotere) chemotherapy. Zytiga inhibits two distinct steps in the production of testosterone from cholesterol even in tumor cells themselves by blocking a cell membrane enzyme called CYP17A1.  Inhibiting one step (lyase) in the testosterone production accounts for the drug’s efficacy but inhibiting the other step (hydroxylase) leads to its side effects. (Therefore it might be advantageous to find a drug that would inhibit only the step that accounts for the undesirable side effects). Zytiga is co-administered with prednisone. For additional information, see Wikipedia.  (Discussed in Jan. 8th, May 7th, June 3rd, and Nov. 21st, 2011 blog posts).

6 – Provenge (Sipuleucel-T); an immunotherapy developed by Dendreon and approved in 2011 by the FDA for treatment of asymptomatic or minimally-symptomatic, metastatic, hormone-refractory prostate cancer. It works by inducing an immune response by activated T-cells in a patient’s immune system against a protein called Prostatic Acid Phosphatase (PAP) which is produced in 95% of all prostate cancers. For a review, see http://www.provenge.com. (Discussed in June 3rd and Sept. 20th, 2011 blog posts).

7 – Xgeva (Denosumab); An injectable, monoclonal antibody approved by the FDA to prevent bone fractures and other skeletal events. In 2010, it was originally approved only in prostate cancer patients undergoing hormonal therapy whose cancers had metastasized to bone. In 2011, its approved use was expanded to include patients with no bone metastases. (Discussed in the October 8th, 2011 blog post).®prostatic hyperplasia (BPH). It works by inhibiting an enzyme called 5-alpha reductase which converts testosterone to its more potent form, dihydrotestosterone (DHT) which is ten (10) times more powerful than testosterone for driving the growth of advanced prostate cancer. (Discussed in the Feb. 25th, 2011 blog post).

9 – Xtandi® (enzalutamide, formerly MDV3100); Approved by the FDA on August 30th, 2012 and Sept. 2014 for treatment of metastatic, hormone refractory prostate cancer patients who have either failed chemotherapy such as taxotere (docetaxel) or who have never have had chemotherapy.  Xtandi disrupts tumor cells’ ability to use testosterone by blocking the cell’s testosterone receptors and prevents the production of androgens within the cell itself. It is an oral, androgen receptor antagonist and does not require co-administration of steroids such as prednisone. It was developed and is distributed by Medivation Inc. (San Francisco, CA) and Astellas Pharma Inc. (Japan). For more information, see the blog posts dated September 14th, 2012 and earlier, viz., June 9th, 2012,  Feb. 10th, 2012, Nov. 21st, 2011, May 7th, 2011 and June 19th, 2014.

10 – Xofigo (previously known as alpharadin); Approved on May 15th, 2013 by the U.S. Food and Drug Administration for use in men with treatment-resistant prostate cancer that had metastasized to bones but not to other organs. Xofigo, administered by injection, will be marketed by Bayer Healthcare Pharmaceuticals who developed the therapy jointly with Algeta, ASA, a Norwegian pharmaceutical company. The drug works by delivering radioactive alpha particles directly to prostate cancer cells that have formed tumors in bone. The radioactive alpha particles from radium-223 dichloride are relatively “heavy” and therefore do not penetrate very far in the body thus limiting the effect of the drug to about a 10-cell radius thereby limiting its toxicity. The drug binds with minerals in the bone to deliver radiation directly to the bones limiting damage to surrounding tissues. For further information, see the June 3rd, 2013 blog post or http://xofigo-us.com. Earlier information can be found in the blog posts dated Nov. 5th, 2011 and Feb. 10th, 2012.

Therapeutic agents not yet approved but under clinical development include:

1 – Ipilimumab; (also known as MDX-101 and MDX-010 and marketed as Yervoy) is a human monoclonal antibody developed by Bristol-Myers-Squibb and approved for the treatment of melanoma. It recently failed to show a response in locally advanced prostate cancer (see April 11th, 2017 blog). It is currently undergoing clinical trials in metastatic, hormone-refractory prostate cancer among other cancers. It works by activating a patient’s own immune system by causing cytotoxic T-lymphocytes to potentially combat tumor cells. (See June 3rd, 2011 blog post.)

2 – Capozatinib (XL184); Exelexis’ drug XL184 has already been approved by the FDA for the treatment of certain thyroid cancers. Phase II clinical trial results showed a decrease in metastatic bone lesions and pain in metastatic, hormone-refractory prostate cancer patients. XL184 inhibits an enzyme called tyrosine kinase which is involved in tumor cell proliferation and invasion, growth of new blood vessels (angiogenesis) and bone metastasis among other processes. Phase III trials are on-going in men who are resistant to Zytiga and Taxotere. These trials will evaluate the control of pain and effects on survival. Preliminary studies of XL184 have shown rapid resolution of pain and rapid disappearance of cancer abnormalities seen in bone scans. (See June 3rd, 2011 blog post).

3 – Orteronel (TAK-700); Clinical development has been discontinued. See July 12th, 2014 post. TAK-700 is a selective, oral, non-steroidal androgen synthesis inhibitor which results in lowering testosterone levels by a mechanism similar to that of Zytiga (abiraterone); it inhibits the enzyme CYP17A1. It is currently in Phase III clinical trials sponsored by Millenium and Takeda Pharmaceutical in metastatic, hormone-refractory prostate cancer patients irrespective of whether they have received chemotherapy with docetaxel (taxotere). (See May 7th, June 3rd, and Nov. 21st, 2011 blog posts). See also Wikipedia.

4 – Prostvac (ARN-509); A therapeutic pox-virus vaccine originally formulated at the National Cancer Institute (NCI) and being developed in collaboration with Bavarian-Nordic A/S. It stimulates the immune system to attack cancerous, PSA-producing cells. It is currently in Phase III clinical trials (PROSPECT, initiated in November 2011) in asymptomatic or minimally-symptomatic, hormone-resistant patients. There is considerable interest in administering Prostvac to patients in earlier stages of disease. It is available in clinical trials. (See Sept. 20th blog post and http://www.bavarian-nordic.com/pipeline/prostvac.aspx).

5 – Galeterone (TOK-011); Discontinued development 8/1/2016; Phase III trials discontinued since drug did not meet its endpoints; see link. In Phase III clinical trials for hormone-resistant prostate cancers. It is being developed by Tokai Pharmaceuticals Inc.  Additional information is  now included in a blog posted on January 6th, 2013. Galeterone, an oral drug also known as TOK-011, is unique in that it is the first and only single-agent therapeutic that combines three distinct approaches to attack prostate cancer and which thereby may help to prevent resistance to ADT. Galeterone works by blocking testosterone synthesis (specifically by blocking the enzyme CYP17 lyase), blocking testosterone’s ability to bind to its androgen receptor and finally, by limiting overall androgen receptor levels in the body. Galeterone’s development and review has received a “fast-track designation” by the U.S. Food and Drug Administration.  For additional information, see the January 6th, 2013 blog and the references therein as well as Wikipedia.

6 – Custirsen (OGX-011); Failed to improve overall survival in advanced cancer patients. See Sept. 4th, 2016 blog. Custirsen is designed to block production of clusterin, a cell survival protein that is over-produced in several cancer types of cancer and in response to many cancer treatments, including hormone ablation therapy, chemotherapy and radiation therapy. Custirsen is an “antisense drug” which short-circuits the production of necessary proteins in a cell thus killing it. The technology is based on using short pieces of single-stranded RNA to bind to a cell’s messenger RNA (mRNA) which is the molecule responsible for shuttling protein-making instructions from DNA in the cell’s nucleus to the ribosome, the cell’s protein manufacturer. Custirsen is in Phase III clinical trials in combination with Jevtana and also in a separate trial (Synergy) in combination with chemotherapy in patients for hormone-resistant prostate cancer.  For further information, see the OncoGeneX website. See also the March 26th, 2012 website entries in the 2012 blog section.

7 – OGX-427: Another drug under development by OncoGeneX. OGX-427 is a second generation antisense drug which, in preclinical experiments, inhibits production of Heat Shock Protein 27 (Hsp27), a cell survival protein found at elevated levels in many human cancers. The Phase II development program for OGX-427 aims to demonstrate inhibition of Hsp27 can lead to improved prognosis and treatment outcomes for cancer patients. For further information, see the OncoGeneX website. See also the March 26th, 2012 website entries in the 2012 blog section.

8 – BIND-014: A nanoparticle delivery system for taxotere (docetaxel) currently in Phase II clinical trials in men with metastatic, treatment-resistant prostate cancer and non-small cell lung cancer. BIND-014 is being developed by BIND Therapeutics of Cambridge, MA. It is described in the December 5th, 2013 blog.

9- Tasquinimod, or TASQ (ABR-215050), is an oral experimental treatment for men with metastatic, treatment-resistant prostate cancer. Chemically, TASQ is a quinoline-3-carboxamide with three-pronged immunomodulatory (activates the body’s immune system to fight cancer), anti-angiogenic (prevents the formation of new blood vessels to feed tumor cells) and anti-metastatic (inhibiting tumor growth) activity. After completing Phase I and II clinical trials, Active Biotech and Ispen, the drug’s developers, announced successful enrollment of 1,200 patients in 250 clinics for a global, randomized, double-blind, placebo-controlled Phase III clinical trial evaluating TASQ in men with metastatic, hormone-refractory prostate cancer. For additional information, see the January 6th, 2013 blog post and the references therein.

10- ODM-201 is currently recruiting patients in a Phase III clinical trial (ARAMIS) in men with non-metastatic, hormone-resistant prostate cancer. It is being jointly developed by Orion and Bayer Pharmaceuticals. It is an oral, androgen receptor antagonist whose mechanism of action is similar to enzalutamide (above). For more information, see the July 7th, 2014 blog and the February 13th, 2017 blog.

11- Fexapotide triflutate; (NX-1207); NX-1207 is a novel drug under development by Nymox Pharmaceutical targeting patients with localized prostate cancer such as those under active surveillance. It can be injected directly into the prostate by a urologist in an office procedure that takes a few minutes, does not require any type of anesthesia or catheterization, and involves little or no pain or discomfort. It is currently in Phase 2 clinical trials. See the following link for more information.

12- Topsalysin; (PRX302); This drug being developed by Sophiris Bio. targets patients with BPH or low- to intermediate risk prostate cancer. PRX302 is a modified recombinant protein engineered to be selectively activated by an enzyme in the prostate, leading to localized cell death and tissue disruption without damaging neighboring tissue and nerves. PRX302 binds to the GPI-anchored receptors on the surface of prostate cells. Once activated by PSA, a protein produced by normal and cancerous prostate cells, PRX302 combines with other activated PRX302 molecules to form stable transmembrane pores that induce cell death. Prostate-specific activation of PRX302 by enzymatically active PSA thus limits exposure of non-prostate tissues to the drug’s activity, the company reports, contributing to the therapy’s safety. It is currently in Phase 2 trials. See the following link.

13- Olaparib: The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to olaparib (Lynparza), an oral poly ADP-ribose polymerase (PARP) inhibitor, for monotherapy treatment of BRCA1/2 or ATM gene mutated metastatic hormone-resistant prostate cancer in patients who received a prior taxane-based chemotherapy and at least one newer hormonal agent.

This list represents a work-in-progress. The reader is urged to seek the latest additional information concerning these agents by inserting their drug names on the various available search engines such as Google, Wikipedia and websites such as that of the National Cancer Institute (http://www.cancer.gov/cancertopics/types/prostate). Additional information including available clinical trials can be obtained from the company websites developing the drugs.

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One Response to Prostate Cancer Drugs Currently Approved or in Late-stage Clinical Trials.

  1. Anonymous says:

    It’s actually a great and helpful piece of information. I’m happy that you shared this useful info with us.
    Please keep us up to date like this. Thank you for sharing.

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