Intermittent ADT May Not Improve Survival In Prostate Cancer Patients

Saw this article today and thought it might be of interest.

HealthDay (4/4, Dotinga) reports, "Advanced prostate cancer patients who are given drugs aimed at lowering their testosterone production to slow the spread of tumors don't get much benefit if the drugs are given only intermittently," according to a study published in the New England Journal of Medicine.

        MedPage Today (4/4, Petrochko) reports, "Average survival for patients" receiving intermittent androgen deprivation therapy (ADT) "was 5.1 years versus 5.8 years in the continuous therapy group (HR 1.10, 90% CI 0.99 to 1.23 for survival with intermittent treatment)." While "intermittent treatment was associated with significantly improved outcomes for erectile function (P<0.001) and mental health (P=0.003) at 3 months of treatment...these improvements did not continue afterward."

        Medscape (4/4, Mulcahy) reports that Maha Hussain, MD, "first presented results from the study - the Southwest Oncology Group (SWOG) 9346 trial - last year at the annual meeting of the American Society of Clinical Oncology (ASCO)." Medscape adds that "at the ASCO meeting, Dr. Hussain said that the findings go against 'conventional belief.'" Hussain "was referring to the fact that many clinicians and academics have believed, on the basis of previous research, that intermittent therapy could prolong disease response, or at least would not be detrimental in terms of survival."

        According to the Oncology Report (4/4, Moon),the "study was funded by the U.S. National Cancer Institute," among others.

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Hi

The guidelines for the testing are out of date I think.

I'm 2 years out from my 2nd 6 months on adt2. intermittent session.

My first was 3 years to a psa rise and now going into my second year.

The guide lines are not current thinking.

No intermittent if your psa doesn't drop below .05 and stay there for several months.

Also never wait till psa rises to "20" to start a treatment.

Any way that's how my oncologists at dana-farber feel. And Dr Strum :)

Best wishes to all the brothers and there family's.

Gerry

    

You have to be careful in interpreting the Hussein study. She looked at men with Stage IV disease who already were diagnosed with distant metastases (M1), often multiple and some in soft tissue as well, as picked up a bone scan. Most of those men had not previously been treated with RP or RT, but all were still hormone responsive. It isn't common to see men like that nowadays, because men are usually picked up earlier in the disease progression cycle.

It seems clear from other studies that Intermittent ADT (IADT) seems to be non-inferior to continuous ADT (cADT) and provides better quality of life when used earlier in the disease progression.

In the following study, they looked at men whose cancer had progressed after radiation, but who had no detectable mets (M0). They found IADT to be non-inferior to cADT:

Intermittent Androgen Suppression for Rising PSA Level after Radiotherapy

The following study of men with aggressive (T3 or T4) disease may help explain the apparent discrepancy. Men with no detectable disease in nodes (N0) or distant mets (M0) were able to stay on and off ADT longer without evidence of disease progression, than men with positive nodes (N1) or positive mets (M1).

Intermittent androgen deprivation for aggressive prostate cancer: 8 years of clinical experience

So, if it were me, I would want intermittent ADT until distant mets were discovered, and continuous ADT thereafter.

Peter,

I think the way the Hussein study worked is that everyone was put on ADT for 7 months to begin with, just to test whether they were hormone-responsive or not. The ones that weren't were excised from the study. The rest were randomly assigned to continuous or intermittent, so the actual study period begins with the continuous sample "on" ADT, and the intermittent sample "off" ADT.

To add to the confusion, I should also cite the Finnish study, which included men who had locally advanced or metastatic PC. They were also pre-tested for hormone responsiveness, but for 2 years. After median follow-up of 65 months after the test period, prostate cancer mortality was similar in both groups, as was median time to death. So in this "mixed" group, intermittent was non-inferior to continuous.

The FinnProstate Study VII: intermittent versus continuous androgen deprivation in patients with advanced prostate cancer.

So many questions remain unanswered, such as: what is optimal timing for IADT? what are the optimal measurement triggers? should 5aris or even testosterone be used in the "off" cycle? how do all the new therapeutic drugs in the last few years change things? and how does the enhanced ability to detect metastases change things? I think the decisions will have to be made on a case-by-case basis for a long time to come.

Peter (cont'd),
As I thought about Hussain's study, I realized that everyone in her study was newly diagnosed, so other than ADT, no one in her study had been treated by surgery or radiation. Therefore, there was no reason to believe erectile function would be impacted at all -- desire/libido, of course, but not the ability to have erections, which is what she reported. Probably, after the first "off" cycle, many men found achieving erections tiresome, and just reported it as diminished erectile function.