Xtandi and Zytiga, The Future is Now

MARK SCHOLZ, MD

There are two new kids on the block, Xtandi and Zytiga. Both medications are real game changers. They are special because they can induce cancer remissions in men whose prostate cancer has become resistant to Lupron.  These pills are so effective that protocols for managing hormone resistant prostate cancer have been completely revamped.  Previously, men with hormone resistance were first treated with Taxotere chemotherapy, typically with undesirable side effects and frequent doctor’s visits.  When men on Xtandi and Zytiga are responding well, since they no longer need an intravenous infusion of Taxotere every three weeks, they only have to come in for a doctor’s visit every three months.

While Xtandi and Zytiga are now FDA approved for hormone resistant prostate cancer, there is no reason to believe they won’t also show enhanced effectiveness against earlier-stage, hormone-sensitive disease as well.  This rationale is based on a long established fact about anticancer treatments in general: “Any treatment that is effective against advanced cancer generally proves to be more effective against earlier-stage cancer.”  This assumption is so logical one might wonder why the academic medical world insists on doing studies to prove it.  Honestly, the biggest barrier is probably cost.  Insurance companies that pay for these expensive medications demand ironclad proof of a beneficial effect before being willing to cover their expanded use.

Physicians, particularly urologists, who are unfamiliar with these potent new agents, are another barrier to the expanded use of Xtandi and Zytiga in earlier-stage prostate cancer.  Urologists, the surgeons who over the last 20 years have only slowly become familiar with how the standard medications Lupron and Casodex function, are often uncomfortable using new agents that can be associated with rare side effects such as high blood pressure, seizures, liver problems and potassium depletion.  To urologists, the doctors who are managing the men with early-stage prostate cancer, Xtandi and Zytiga are relative unknowns.

In spite of all these barriers, the logical place to consider using Xtandi and Zytiga is in earlier-stage, “high-risk” situations which have suboptimal cure rates with Lupron alone.  The situations where this might apply are listed below:

·         Newly-diagnosed men with a PSA over 20 and a Gleason score over 8

·         Newly-diagnosed men with seminal vesicle invasion or pelvic lymph node metastases

·         Relapsed men after surgery with a PSA doubling < 3 months having salvage radiation

·         Newly-diagnosed oligometastatic disease undergoing radiation to all sites of disease

In all these situations, Lupron is known to be beneficial.  In some cases, the addition of Casodex to Lupron further increases the anticancer effect over Lupron alone. This is an important observation because compared to Xtandi or Zytiga, Casodex is a very weak anticancer agent.  Substituting these far more potent agents for Casodex is very likely to result in substantial improvement of the anticancer benefit and is a logical consideration for men who want to optimize their cure rates.