SLIDES & TRANSCRIPTS
Saturday, December 6, 2003

PSA Kinetics in Patients with Hormone Refractory Prostate Cancer

Kenneth Pienta, M.D.

Before I do that, I want to just mention two things. This is obviously a very exciting subject, and General Urology is publishing a supplement in late December that looks at the subject of rising PSA and potential treatments for rising PSA, all the way from patients who are just diagnosed to those that are hormone refractory, so look for that coming up soon.

Before I talk about the hormone refractory population, I have just a couple of slides talking about a national trial that is looking at this group of patients that are hormone naive, that have high risk of dying from their disease.

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This gentleman is eligible for this phase three study 0014 which is opened as an inter-group study as well as through the CTSU. It is phase three study that looks at the impact of early chemohormonal therapy in patients with a rising PSA after primary treatment. So patients who had originally a Gleason score of seven or more, a PSA of two and a doubling time of less than eight months are either randomized to hormonal therapy until failure and then a standard medical care, including chemotherapy, afterwards -- this is the traditional way things are done now -- or arm two, which is four cycles of immediate chemo hormonal therapy, then the patient stays on hormonal therapy, and when they fail that, they are allowed to undergo standard medical care. This trial is open to accrual.

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Again, it is patients who have failed local treatment. They have to have a doubling time of less than eight months and no clinical evidence of disease.

The interesting thing about this trial is that it is designed to be very user friendly. Just about every kind of androgen blockade is eligible. Many different chemotherapies are eligible. We have not locked in one specific regimen because the idea is that this is a proof of principle trial for chemotherapy making a difference early on in patients who are at risk of dying of their disease.

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I'm going to switch topics now after that advertisement about 0014 and talk about what happens to PSA doubling time as a patient transitions between hormone naive prostate cancer and hormone refractory prostate cancer.

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We looked at 208 patients at the University of Michigan grouped by disease progression and treatment, hormone naive versus hormone refractory, but really I have been following in my clinic over the last several years, and looked at their doubling time using traditional calculations.

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What we found was that if you looked at these 208 patients and looked at their average doubling time when they were hormone naive, this was before they started hormonal therapy, in the 200 patients, the average doubling time was just under 36 weeks. There was a wide variety in the range, but the average was 36 weeks.

Now, when we looked at their doubling time as they became hormone refractory, so at this point, hormone refractory one is when they started some form of therapy for failing androgen ablation, their doubling time had decreased to 16 weeks. So the difference here is 36 weeks down to 16 weeks.

Then we wanted to know what happens to doubling time over multiple treatments. What we did was, we looked at the doubling time prior to starting each new therapy, and we found that for the majority of patients, even as they progressed through multiple treatment regimens, their doubling time remained consistent at somewhere between 10 and 15 weeks. At the very end of their treatment, and there are fewer patients out here, so I can't pay too much attention to here, but their doubling times near death approached the six-week range.

So the main message that I have that is somewhat new is that the doubling time in the hormone naive population is 36 weeks and the hormone refractory population, much closer to 16 weeks.

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We also looked at what happens to PSA in the last year of life.

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As we all know, it is I think intriguing that there is no absolute PSA number that equals death, no PSA number that equals symptoms. So we looked at patients in the rapid autopsy program at the university to look at their absolute PSAs, as well as what happened in that year of death. This is just showing you that the PSAs are all over the place.

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what you see is, there is a group out of the 29, four, that have a fairly standard increase, all the way from 12 months before all the way through death.

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We looked at the raw data of 29 patients. This is the raw numbers over time. In general, there is a rapid increase in the last three months, and it looks like it makes sense, it looks like everybody is having an increase.

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But if you actually look at these patients closer -- and this is the log data --

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There is another group that is essentially stable,

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and then there is another group that is stable and then increases,

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and then there are some patients that actually decrease, especially in the last three months of life.

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So I have had to throw out a lot of what I learned about PSA and PSA doubling time over the last couple of years, as we learn more and more about the data. I think that what I have learned is that the PSA, especially in patients with hormone refractory disease, especially in the last three months, becomes totally unreliable, and we can't use that as a guide to therapy.

Thank you.

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