So, let's talk about the mechanism of action with these drugs. So, speaking of Nubeqa for instance,
you know we say systemic therapy which means it runs through the blood, so it's looking for these
little metastatic sites. What is happening when that treatment does reach that metastatic site?
Well, if we go back to the M0 the other really big component, of course, is these men have been
on Lupron, they've had low testosterone usually for many many years and, now ths PSA's going up,
the cancer is growing with—we thought—without any testosterone. Well, it turns out research
indicates that these cancer cells have figured out how to make their own testosterone. So, just
blocking the testicular production of testosterone with Lupron isn't going to do the trick anymore,
and so researchers develop these second-generation hormonal agents that block the synthesis or block
the action of testosterone inside the cancer cell and that's why they're so revolutionary. My
business model as a medical oncologist treating exclusively prostate cancer really changed when
these medicines first came out in 2010. We used to give a lot of chemotherapy to these patients
and these second-generation hormonal agents are so effective; men are going into remissions
for extended years and thankfully don't need chemotherapy, and this is why it's important to
look at the side effect profile of these medicines because since they're effective for years
if they cause bad side effects that can you know affect a patient's quality of life.
Well i think it's interesting, you know, since they all kind of have
a similar way of working and they seem to be in similar time frames as far as
results, really what it seems to come down to with these side effects is quality of life. So,
you've mentioned these four, you know, drugs. Can we talk about the side effect profiles of
each and what you think would be more beneficial in certain cases?
Yeah, they all seem to be equally effective and so if you're looking at cost
since Zytiga has become generic, it is the least expensive. It's a little more cumbersome;
you have to take some prednisone with it, monitor the liver function, make sure that there's no
mineral abnormalities in the blood, but it's quite effective. And then if you look at the other three
medications Xtandi, Erleada, and Nubeqa, Nubeqa seems to come out ahead of the pack because it
doesn't have the same propensity for causing rashes that we see with Erleada and it
doesn't have the same predisposition to causing fatigue which we can sometimes see with Xtandi.
There's another advantage to Nubeqa and that is that in patients that are taking other pills
it seems that Nubeqa is less likely to have interactions with other types of pharmaceuticals.
So, Nubeqa seems to be a very attractive medication for this particular space. Xtandi and
Erleada have broader approvals for other stages of prostate cancer and you hear about them more
but for someone who has this M0 type prostate cancer, Nubeqa is approved specifically for
that and it's probably got significant advantages over the other alternatives.
So, this is a very specific question but I've had multiple patients ask it,
you mentioned that there were really no negative interactions when it came to Nubeqa compared to
other drugs. In regard to heart issues, does it matter between any of the other
drugs? We get a lot of patients that come in and say i'm taking Erleada or Xtandi or
Nubeqa and all sorts of things and they have some sort of heart issues and they're concerned.
So, is there any of those four that would work better in those cases?
Well, a concern with, of course, heart issues come in all sizes and shapes, but Zytiga
can cause fluid retention. So, if people have a history of congestive heart failure,
you have to be quite judicious if you're going to use Zytiga,
The other three are fine and, you know, the other issue on the table, of course,
if someone has a history of seizures they're supposed to stay away from Xtandi.
So, speaking of the side effects of all four, actually, we have some very practical
tips that we've talked about at PCRI and the conferences with you and Dr. Moyad
in order to help mitigate these side effects. So, you know, you talked about weight training. Can
can you talk about those different things that help mitigate side effects of hormone therapy?
Well, I would emphasize just that one thing because when you block a man's testosterone
they tend to lose muscle and people feel weak, tired, depressed. This issue starts
long before these medicines because you can't be in the M0 space unless you've been on Lupron or
one of the analogs of Lupron, you know, there's Firmagon and Eligard and Trelstar,
and there's a new medicine coming out, relugolix, that will do the same things. So anytime
a doctor proposes some sort of testosterone blockade, the family, the men, everybody,
the doctors should be thinking, "okay where are we going to get this patient to a weight
training program and help him feel reasonably normal while he's taking these medicines."
So, in order to be in the M0 space you have to have a rising PSA on Lupron,
so what is the PSA going to look like after these treatments?
So, the results are usually surprisingly good and our hope is that the PSA will return to
undetectable levels within a couple to three months, four months of starting these medications.
One thing that's interesting is that in the clinical trials evaluating the effectiveness
of second-generation hormonal agents for M0, the average starting PSA was around 10, and I
don't know why they waited so long to get going on these medicines because if people are using
ultrasensitive PSAs on Lupron, you can detect hormone resistance in someone's PSA who goes from
0.1 to 0.2 to 0.3, and you can be quite confident that hormone resistance is occurring and it's time
to make a change in treatment. The results of the second-generation hormonal agents and some
of the rising PSA are far superior when the PSA is less than one compared to say 10 or higher, and so
patients and doctors need to be vigilant when someone's on Lupron if the PSA starts rising. They
need to make a switch quickly and not wait around as was done in these clinical trials. I'm not
sure what was happening; maybe people didn't believe in these second-generation agents and
they weren't that motivated to get going, but now we know they work really well.
Hi everyone, this is me and Hunter. No we did not name him Prostate or Gleason,
but thank you so much for your comment recommendations.
Well, we're just here to say subscribe to our YouTube channel—you want them to subscribe,
yes you do—and visit our website pcri.org for more information we hope you have a great week!