Please note that this summary only contains information from the full scientific abstract: View ESMO Scientific Abstract

Studies in mice to look at why apalutamide but not enzalutamide can cause skin rashes

Date of summary: September 2019

The full title of this abstract is: Enzalutamide (ENZA) and Apalutamide (APA) In vitro chemical reactivity studies and Activity in a Mouse Drug Allergy Model (MDAM)

The study drugs are approved to treat the condition under study that is discussed in this summary.

 

Researchers must look at the results of many types of studies to understand whether a study drug works, how it works, and whether it is safe to prescribe to patients.

This summary reports the results of only one study. The results of this study might be different from the results of other studies that the researchers look at.

 

More information can be found in the scientific abstract of this study, which you can access here:
View ESMO Scientific Abstract

What did this study look at?

  • Prostate cancer is one of the most common cancers in men.
  • Prostate cancer cells depend for their growth on male sex hormones (called androgens).
    • Treatment for prostate cancer involves lowering the amount of androgens in the body through surgical castration or androgen-deprivation therapy (known as chemical castration).
  • In some men, the cancer may not respond to androgen-deprivation therapy and will continue to grow, even without androgens.
    • This type of prostate cancer is known as castration resistant prostate cancer (CRPC for short).
  • Enzalutamide (ENZA for short) and apalutamide (APA for short) are approved treatments for CRPC.
    • APA is only approved for CRPC that has not spread to other parts of the body.
  • Although these two drugs work in a similar way, they have different chemical structures.
    • As a result, ENZA and APA may behave differently in the body.
  • In previous studies, men who took APA had an increased risk of developing a skin rash compared with men who received a placebo. However, in other studies, men who took ENZA did not have increased risk of developing a skin rash.
  • In this study, researchers wanted to find out why men who take APA have an increased risk of developing a skin rash.
    • Researchers think that a group of chemicals found on APA, called cyanopyridines, causes the skin rash in these men.
    • ENZA does not contain cyanopyridines.
  • Researchers tested the immune reaction of APA and ENZA in laboratory tests and in a mouse model.
    • The experiments help researchers to find out how the human immune system may react.
  • Researchers wanted to know if the body’s immune system could be reacting to the cyanopyridines on APA, causing the skin rash.
  • This summary describes the results from these experiments.

Who took part in this study?

  • Researchers first mixed APA with glutathione, a common chemical in mammalian cells, to see if APA caused a chemical reaction in lab tests.
  • Researchers then mixed APA or ENZA with human and mouse blood, to see if these drugs reacted with blood proteins.
  • Researchers then treated mice with APA, ENZA, or a third compound called RD162, to see if any of them caused an immune reaction in mice.
    • The mice received 3 different doses of the study compounds.
      • The mice were looked after in line with national guidelines to minimize pain and discomfort during the experiments, and were humanely killed.
    • Six days after treatment, researchers isolated glands containing immune cells (called lymph nodes) from the mice and counted the number of cells.

What were the results of the study?

  • The lab tests suggested that the cyanopyridines on APA react with a specific group on glutathione.
  • The researchers found that APA reacted with mouse and human blood proteins, but ENZA did not.
  • Mice treated with APA had increased numbers of cells in their lymph nodes, suggesting that they had an immune reaction.
    • The larger the dose of APA, the more cells were found in the lymph nodes.
  • Mice treated with ENZA or RD162, both of which lacked cyanopyridines, did not have increased numbers of cells in their lymph nodes.

More results from this study can be found here:
View ESMO Scientific Abstract

What was the main conclusion reported by the researchers?

  • In this study, researchers found that the cyanopyridines found on APA may ‘turn on’ an immune response in mice.
    • This immune response may explain why some men with prostate cancer who are treated with APA have an increased risk of developing a skin rash.

Who sponsored this study?

Pfizer Inc.
235 East 42nd Street NY, NY 10017
Phone (United States): +1 212-733-2323

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