Starting Treatment Early for Metastatic Prostate Cancer: Part III

In Part I and II of this series of articles, the effectiveness treatment initiated at an earlier stage, with either Lupron or Provenge, was compared with the effectiveness of either agent when started at a later stage. With both types of treatment, starting the therapy at an earlier stage resulted in a significant enhancement of the anticancer effects.  Similarly, recent studies evaluating the effectiveness of starting Taxotere at an earlier stage show the same thing.

Taxotere has been the go-to chemotherapy for advanced, hormone-resistant prostate cancer for over ten years. It was approved by the FDA in 2004 after being proven to prolong survival. Prior to the FDA approval of Taxotere, the only available chemotherapeutic agents (Novantrone, Emcyt and Velban) were of borderline value. For example, Novantrone could reduce pain and improve quality of life. However, it had no impact on survival. Taxotere was FDA approved after two large randomized trials confirmed a survival advantage, however, the amount of survival improvement was relatively small, only in the order of a few months.

For years, experts have been wondering about the optimal timing for using Taxotere. Should it be started after resistance to Lupron develops or would it be more effective to start before the onset of hormone resistance?  Since the original studies leading to the FDA-approval of Taxotere evaluated its effectiveness in men who were already Lupron-resistant, the general policy adopted by physicians has been to withhold Taxotere until Lupron becomes ineffective.

Doctors would reason as follows: “Since Taxotere has various side effects, and also, since there is no proof that earlier treatment is more effective, we will only recommend initiating Taxotere after Lupron stops working.”  

It is well known that most men with metastatic prostate cancer eventually develop hormone resistance.

Therefore, since earlier treatment is often more effective, it would be logical to consider attacking the disease before hormone-resistant cells multiply further and mutate into treatment-resistant clones. In 2014 and 2015 the results of two clinical trials testing this premise were published. The first study, CHAARTED (Chemo-hormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer), was presented at 2014 annual meeting of the American Society of Clinical Oncology (ASCO) and published in the New England Journal of Medicine in 2015. It demonstrated that for men with newly-diagnosed hormone-sensitive cancer, in patients who had already developed metastases, the addition of four months of Taxotere started in conjunction with Lupron markedly improved survival compared to men who started Lupron alone and then started Taxotere when the Lupron stopped working. In this study, the survival of the men treated with Taxotere at the same time as Lupron was 18 months longer than the men who were initially treated with Lupron only.


The results of another, similar trial, called STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy trial), were presented at the 2015 ASCO meeting. In this study of almost 3000 newly-diagnosed, hormone-sensitive men, half of the men were given immediate Taxotere plus Lupron. Their survival was compared with the other half who were initially treated with Lupron alone. Just like in the CHAARTED study, this second group was treated with Taxotere after the Lupron stopped working. And again, just like with the CHAARTED trial, men who started Taxotere prior to hormone resistance lived significantly longer.

So while earlier Taxotere is now the newly-established norm, in the day to day management of patients with prostate cancer, the way other types of new treatment (such as Zytiga, Xtandi, Xofigo and Jevtana) are selected often follows a well-worn, sequential pattern. Using medications out of sequence or in combination is frequently frowned upon. The common approach defaults to the, “It’s always been done that way."  Doctors use this excessively conservative thinking for many reasons and don't always evaluate “outside the box,” treatment approaches. However, especially now that so many new and effective agents are being FDA-approved, using treatments in a pedantic sequential manner may fail to maximize the potential of these new anticancer tools. Part IV of this series on early treatment will present some ideas how one might consider using these new treatments in a more effective manner.

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