So, in general, first of all let me preface this
um-hmm
I remember 10, 15, 20 years ago, you know, people talk about chemo and they still do as if this
archaic thing and I can't wait to move beyond chemo, they're just giving chemo, you know, it
kind of has that negative symbol; it still carries that negative symbol, but what's amazed me about
chemo is that negative vibe that had been thrown out there for so long, well in testicular cancer
and now including in prostate cancer, it really has a dominant place, and can you explain that?
What I mean by that is it — I'm so amazed at how twenty years later, it is such a dominant
part of the conversation including in aggressive disease, then what's your general recommendation
now someone's diagnosed or is on different drugs? I mean is this as simple as anyone sitting down
going, "Hey, I'm somewhere here in the spectrum of prostate cancer, do I qualify for chemo because
chemo seems to be used in various points?" I mean, what do you say in a consult like that? Yeah.
So, let's just clarify first the term chemo or chemotherapy. If you really break it on down,
chemotherapy just describes any sort of drug therapy. Taking aspirin is chemotherapy, but in
the realm of oncology when we say chemotherapy, when a patient hears chemotherapy they're
really thinking about what we call cytotoxic chemotherapy. So, basically it's a drug that
we give that non-specifically kills cells. Now, it kills more specifically rapidly growing cells and
the thought is that cancer grows more rapidly than normal cells do, so you get more focused toxicity
against the cancer cell than you do against your own cells, but that also kind of explains why many
of the toxicities we get which are like GI-related toxicities, oral ulcers, those sorts of things,
they have to do with areas that are rapidly growing cells like hair loss, etc. Hair cells or
hair is very rapidly growing so, you know, that's what we're talking about when we're talking about
chemotherapy. I think the reason chemotherapy had a bad name is because of this non-specificity.
People like the idea, the approach, of finding a gene defect and going after it.
Right.
, and the field has changed a lot. Not just prostate cancer, but a lot of diseases have
changed a lot where we do have a lot more of these drugs. I think that it doesn't mean that
we should forget about chemotherapy. Chemotherapy still has a strong role in these diseases and in
prostate cancer, as you mentioned, with some of the data with the use of docetaxel early
in metastatic hormone-sensitive prostate cancer we can see an additional median—at the middle—a
year and a half to two years survival benefit whereas if you use it late for palliative effect,
it's not nearly as dramatic. There's still a role for chemotherapy; it's not always the end-all
be-all and there might be a day in the future where we're not using as much chemotherapy and we
certainly are getting smarter; we're understanding the biology better, we're developing newer better
drugs that are more targeted and focused, but it doesn't mean that we should forget about chemo.
So which came out — there's two chemos fda-approved for prostate cancer at some point,
right? There's Taxotere, it's here, right? And then there's Jevtana. Now, again I'm just using
trade names because patients and a lot of people understand trade names, you know,
the generic names makes people nuts. Sure.
Me too.
So, Jevtana and Taxotere, is there any situation where you see either some kind
of third one offered, or Jevtana offered first? In other words, a lot of patients will say, "Hey,
Jevtana, the second one seems to come with less side effects, why don't we use that first? Why
don't we use Taxotere?" Can you explain which one they're using first, which one
they're using second, and do we see possibly a third one or more in the future coming at us?
Yeah, so Jevtana that's cabazitaxel and Taxotere is docetaxel, so right now docetaxel is being
used in two clear disease settings. One is for a new metastatic disease that
still castration-sensitive or hormone-sensitive testosterone lowering agent-sensitive and combined
with the testosterone lowering agents, and that's where I said there's a dramatic survival benefit.
Yeah.
It can also be used for a metastatic—what we call—castration-resistant prostate cancer where
patients have already received testosterone lowering therapies and the disease has shown
progression through that, and that's called metastatic castration-resistant prostate cancer.
In that situation, it also offers survival benefit, but it also offers pain palliative
benefits. So, in that situation, I tend to use the docetaxel a little later because the survival
benefit is not as dramatic and I'm not going to improve somebody's pain or quality of life if
there is asymptomatic, okay. So I tend to utilize it when they have more symptoms. Jevtana or
cabazitaxel is now fda-approved after that, so for patients who have received the docetaxel/Taxotere
and usually the patients have received a novel hormonal agent like abiraterone or enzalutamide,
something like that as well, and that's where Jevtana is FDA approved. The reason
Jevtana is not used first line is for a few reasons. When it first came out, it had a lot
of toxicity. There was a 7.5 percent febrile neutropenia rate and. 4.9% toxic death rate,
but that's because it was a new drug, we didn't quite know how to use it as well, we weren't
using growth factors to prevent infections in the very first cycle, right off the bat,
and the dose was probably a bit high. It was 25 milligrams per milliliter squared. Subsequently,
there has been a study that I mentioned in my talk that showed that 20 milligrams per
milliliter squared works just as well for survival and has less toxicity. So that's what I use,
and I think that the 25 is more toxic than docetaxel but the 20 is less toxic than
docetaxel. However, there was a study that compared the docetaxel and cabazitaxel (the
Taxotere and the Jevtana) head-to-head and they did —it's called the FIRSTANA study—and
it didn't show benefit with cabazitaxel being better, hence, that's the reason why people
are still using Taxotere (docetaxel). first and the Jevtana later, after that.
I think to answer your last question there in regards to other cytotoxic chemotherapies,
Yeah.
I think the other situation where there's another cytotoxic chemotherapy that's going to get more
attention is an old drug called carboplatin. That's just a platinum chemotherapy, it induces
double-strand DNA breaks for patients who have DNA repair deficiency which I talked about with the
PROFOUND study of the PARP inhibitors. These drugs cause breaks in both strands of the DNA and if you
also have a gene mutation and a DNA repair gene, those cancer cells just aren't able to repair that
very well and it's exquisitely sensitive and seems to work well in that patient population,
and you know, Heather Chang is one of our junior colleagues here (she's actually
becoming an associate professor now, so not so junior anymore) but she's really led the charge
in studying that in a man with metastatic prostate cancer and DNA repair deficiency.
That's the third one that I hear so much about the carboplatin, right?
mhm
You see that — I want to be optimistic that's gonna get
approved somewhere down the road on some level. Do you feel that way?
Well, I don't think it's a drug that's going to get
approved because to get approved requires that somebody actually—
Does a trial
Right, somebody actually puts a lot of money and resources into getting it through the
FDA. I think it's a situation where we just need more data. It's not an expensive drug;
it's an old drug that's available, it just will be repurposed in this setting, and I don't
think that you always need to have regulatory approval. So, you have me on camera on record
saying that. I'm a friend of the FDA, please don't be angry at me if you're listening, but...
No, but there are people who clearly get it in oncology offices around the world
including in the United States and they get responses to it...
Correct
...You answered the question that what I really want patients to understand which is you have two
of them and you have one that someone oncologists use now "carbo," they call it carbo, carboplatin,
and some people get responses to it which is pretty awesome. So that's great. So,
anything else in chemo that we didn't cover in
terms of what's happening that what people have to their beck and call?
I think those are the highlights right now, so I think you covered it pretty well.