Starting Treatment Early for Metastatic Prostate Cancer: Part IV

Recently, many new anticancer agents have become available for the treatment of prostate cancer—Zytiga, Xtandi, Xofigo, Provenge and Jevtana, but differing opinions about optimal combinations and sequencing will naturally arise.  If we adopt the belief that treatment effectiveness is enhanced when used against earlier-stage cancer, thoughts are engendered about using two or three treatments simultaneously.

In most instances, studies evaluating the effectiveness of these agents when used in combination are lacking. However, in some cases small phase II studies have been complete that demonstrate that combination treatment can be administered without excess toxicity.

Giving treatments one at a time (rather than using treatment combinations) has long been the preferred approach by academicians (the academia doctors that have major influence over how prostate cancer is treated). The academicians are paid by pharmaceutical companies to test one treatment at a time. This “one-treatment-at-a-time" approach enables the university doctors to accurately evaluate each drug for its anticancer effects without introducing potentially confounding variables that could skew the accuracy of the results.

Therefore, the “standard operating procedure,” based on longstanding past policy, favors the sequential, one-treatment-at-a time approach.

However, if one likens metastatic cancer to a fire burning out of control, to maximize survival, every effective agent within reason should be brought to bear without delay. If firefighters have three firetrucks at their disposal they would never consider holding one firetruck in reserve, waiting to see if the fire could be extinguished by using only two trucks!

The fire is fought with a maximal up-front effort using every possible resource to extinguish the blaze.  Possible exceptions to this “all out approach” include financial constraints, concerns about unacceptable toxicity, or, perhaps in the case when the patient is excessively frail or elderly.

The rationale for the combination approach is based on the multiple clinical observations cited in Part I II, and III of this series of articles that who how treatments generally work much better against early-stage cancer.  A couple of mechanisms explaining why earlier treatment works better are presented in those previous articles. Another likely explanation is that as the cancer progresses, it develops stronger countermeasures that disable how the immune system would normally fight the cancer. Therefore, using treatments at an earlier stage, in combination (rather than sequentially) brings more anticancer firepower to bear.

Experience using treatments in combination is still lacking. Nevertheless, the following list presents some considerations about how the available agents might be combined.

Preliminary trials using some of these agents in combination indicate that the potential side effects are not associated with unreasonable problems assuming they are administered under the supervision of an experienced oncologist.

·     Taxotere combined with Zytiga or Xtandi

·     Provenge followed immediately by Zytiga or Xtandi

·     Xofigo combined with Zytiga or Xtandi

·     Xofigo combined with Taxotere

·     Zytiga combined with Xtandi

Other combinations can also be considered as this list is by no means exhaustive. Men who face a more serious type of prostate cancer should not let conventional treatment approaches constrain their freedom to use more than one therapy at a time. The risks and benefits of combination therapy and the uncertainties that are involved can be reviewed with their physician before any treatment is initiated.  Sometimes when doctors are in unfamiliar territory the prudent approach is to start one therapy first and then add a second therapy slowly at a lower dosage and slowly escalate the dose after the patient’s ability to tolerate the combination has been established.

The field of prostate oncology is entering a new era with the availability of many diverse and efficacious agents. The old way of practice that relied upon using one treatment at a time needs to be seriously reconsidered in light of the opportunity we have for substantially prolonging life. Unwillingness to venture into uncharted territory is likely to result in a real disservice to the men who seeking an all-out effort from their oncologist.   

Continue Reading