“First do less harm” … a significant unmet need

It is now some 70 years since Huggins and his colleagues in Chicago first showed that surgical castration (orchiectomy) could be used alleviate (palliate) the bone pain associated with metastatic prostate cancer. This was the beginning of the use of “hormone” therapy — more appropriately known as androgen deprivation therapy or ADT — in the management of prostate cancer (by manipulation of the male endocrine system), and it is still the type of treatment at the very heart of the management of advanced forms of prostate cancer.

In January this year, a group of clinical researchers in London, England (Bourke et al.) published an article in the British Journal of Cancer arguing that it was high time that we instituted “a comprehensive research strategy” designed to reassess the entire use of androgen deprivation in the management of progressive and metastatic forms of prostate cancer.

Bourke et al. argue (correctly) that “modern” prostate cancer — at least in the developed world — is a very different disease when compared to the type of prostate cancer to which ADT was originally applied, when most patients were diagnosed with symptoms of advanced or metastatic disease, and curative therapy was impossible for the vast majority of these men.

Most customary and widely used forms of ADT expose patients to significant side effects of treatment and serious risks associated with metabolic syndrome — and yet they offer a very limited survival benefit. There is a strong argument to be made that — despite the recent development of new ways to manipulate the endocrine system (with drugs like degarelix and abiraterone and enzalutamide) — we are still far from knowing how best to apply ADT in the treatment of prostate cancer in ways that will maximize a patient’s survival and optimize his quality of life (by minimizing the side effects of therapy).

The development of “a comprehensive research strategy” to re-think the application of ADT in the management of prostate cancer today would be laudable. The ability to implement such a strategy amid the competing interests of all the relevant parties may prove more challenging.

4 Responses

  1. HIFU also treats bone pain from metastatic cancer, without side effects. Don’t remember where I read it, maybe here?

  2. Ron:

    A form of HIFU, using InSightec’s ExAblate technology, has been approved by the FDA for the treatment of pain caused by metastases to bone. I have not seen clinical data on outcomes after such treatment (yet), so I am not sure it is appropriate to claim that it is “without side effects.”

  3. Yeah!! Somebody finally gets what is like to be 56 years old and living in a Lupron cloud. All the good news coming out is great but the reality for some of us living a longer compromised life is not all it is cracked up to be … but the alternative is not great either, so we keep on keepin’ on. …

  4. What Bill said.

    Many men can tolerate Lupron/ADT reasonably well, experiencing “only” hot flashes, diminished libido, erectile dysfunction, weight gain, and sluggishness; they tend to be the ones who share their experiences.

    Those of us who slip into depression, anhedonia (inability to experience joy) and aboulia (inability to will) aren’t much heard from. I was 51 when I had my first bout with Lupron.

    After my year-plus of zombiehood, when I had regained the interest and ability to read and understand an Explanation of Benefits form, I had a sardonic laugh at the classification of Lupron as a “palliative”.

    So far, I’ve never experienced any symptoms from cancer itself; but the treatment was one of most identity-destroying I’ve ever endured. Palliative, indeed.

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