Testosterone Inactivating Pharmaceuticals (TIP)

BY MARK SCHOLZ, MD

Hormones play a large role in cancer growth.  They are also integral to treatment.  Testosterone is a key player. It originates mostly in the testicles and, to a lesser degree, the adrenal glands.  Testosterone causes the common male characteristics such as bigger muscles, facial hair growth and heightened sex drive. Testosterone is essential for prostate cancer growth.

Blocking Testosterone Kills Prostate Cancer

Hormone therapy works by blocking testosterone.  When prostate cancer cells are deprived of testosterone, apoptosis occurs, meaning the prostate cancer cells commit suicide of their own free will.  The amount of cell death is usually dramatic.  Studies evaluating the amount of tumor shrinkage occurring in prostates in men receiving TIP prior to surgery commonly show a dramatic downsizing of the tumor.

A protein located inside the cell called the androgen receptor is the mechanism by which the cell responds to testosterone.  When the androgen receptor comes in contact with testosterone, it migrates into the cell’s nucleus where it interacts with DNA to stimulate cell growth and replication.

 Various Mechanisms for Blocking Testosterone

Lupron, Zoladex, Firmagon, Eligard and Trelstar indirectly block testosterone by inhibiting the pituitary gland, which normally stimulates the testicles to produce testosterone.  Other medications such as Casodex, Nilutamide and Flutamide block the androgen receptor directly.  Zytiga, Erleada and Xtandi more potent agents.  Zytiga inhibits cancer cells from making their own testosterone.  Erleada and Xtandi work by blocking the activity of the androgen receptor.

The Type of TIP Depends on the Cancer’s Stage

TIP’s efficacy is influenced by the type of medicine, how many medicines are used, and the duration of therapy. Higher stage cancers require more potent therapy. A man’s stage is assigned by answering the questions in the staging quiz available at www.prostateoncology.com.

Medical skill and experience is required to fine-tune the selection and duration of TIP. Nevertheless, here are some rough guidelines:

  1. Men with High-Teal who are undergoing radiation often begin TIP two months before starting radiation and continue for a total of four to six months of therapy.  Treatment for Low-Azure is the same as for High-Teal.
  2. Men with Basic-Azure and High-Azure are typically treated with TIP for 18 months.  Treatment starts two months before radiation and continues during and after radiation.
  3. Men with relapsed disease (Indigo) often receive intermittent TIP.  An initial course is 6 to 12 months.  After stopping, PSA levels are monitored every 3 months.  Cycle #2 starts when PSA rises between 3 and 6.
  4. With occasional exceptions, men with Royal remain on TIP continuously.
  5. Men with Royal who become resistant to Lupron are usually administered Xtandi, Apalutamide or Zytiga. Treatment is continued until there is clear evidence of new metastases on a bone scan or body scan.
  6. TIP plays a role in shrinking an enlarged prostate gland prior to a radioactive seed implant.  Without this shrinking, some men with excessively large prostates would be ineligible for seed implantation.
  7. TIP can be used as a primary therapy instead of surgery or radiation to treat men with Teal.
  8. TIP can be used after surgery in men with Azure.  This is controversial.  Some older studies showed no improvement in cure rates.  However, those studies used a mere three months of TIP and only evaluated men with Teal.  Subsequent studies using TIP for a longer duration in men with Azure showed improved survival.

Side Effects

TIP is far more effective than almost any other cancer therapy available for any type of cancer.  However, hormonal therapy causes wide-ranging side effects.  We recommend careful review of our brochure on how to reduce the side effects of TIP.  Due to TIP’s potential for notable side effects, it should be used judiciously.  Therapy should continue no longer than what is necessary to obtain a maximal anticancer benefit.

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