“Shocking Away Melanoma”
Adil I. Daud, MD
Adil I. Daud, MD, Medical Oncologist, University of California, San Francisco, talks about a new
treatment that is “shocking” away melanoma.
Is the advanced stage melanoma hard to treat?
Dr. Daud: It is very hard to treat. If you look at the statistics from a few years ago, only about 10
to 15 percent of patients with advanced stage melanoma would be alive at 5 years. Now, I think
the numbers are better.
Why is it so hard to treat?
Dr. Daud: I think part of the problem is that it isn’t sensitive to chemotherapy. If you look at
other cancers like breast cancer or colon cancer, where we’ve made big advances, I think those
have been cancers that are very responsive to chemotherapy. So, you can eradicate a good
portion of the cancer at the time of surgery, or after surgery, and so you can keep a lot of those
patients from coming back and developing advanced cancer. In regards to melanoma, the
problem has been that we’ve tried again and again with different types of chemotherapy and it’s
just not a chemo sensitive tumor. The response to chemotherapy has been in the ten percent
range, where ninety percent of patients don’t have a response. When you’re trying to cure a
disease with a ten percent response rate, chances are you’re missing a lot of cells. Those cells
can start dividing and cause problems.
Targeted therapy has been a big advance, but the problem with targeted therapy has been that
ultimately a lot of people will develop resistance to targeted therapy. It starts off working great,
but six months or nine months later people will develop resistance to it and so their tumors will
start growing again. Another big advance in our field has been in immunotherapy, harnessing
the body’s immune system to fight these tumors. So, that’s been super successful I would say. I
think there are still some challenges in immunotherapy. There are autoimmune side effects that
immunotherapy can unleash and so you’ve got to control those autoimmune side-effects so that
you know they don’t affect the person’s quality of life a whole lot. Another problem with
immunotherapy is that even today; only a certain number of patients will respond to
immunotherapy, for the other 40 or 60 percent of folks, we don’t know why exactly their immune
system is not recognizing their melanoma.
Is it a frustrating cancer to treat?
Dr. Daud: It is a frustrating cancer to treat and it’s also very resistant. Often times the cancer
will evolve. People say that they are smart tumors and there are dumb tumors and melanoma is
definitely one of the smart tumors that finds ways around a lot of treatments.
How are electro impulses changing the game?
Dr. Daud: The way electro impulses are changing the game is at the point where you have
melanoma that’s spread, but it’s still accessible to the surface. For instance, if it’s under the
surface of the skin, in lymph nodes, or in a place where you can reach, like your chest wall,
thigh we can actually deliver genes directly in to the tumor. You can pick whatever gene you
want, but the one we focused on is the gene called interleukin 12, which is a molecule that the
immune system uses to signal danger. The melanoma tumor now has this giant flashing light on
it that makes it visible to the immune system. So, it makes your immune system see that that’s
all is not well, you know, stream in to the tumor and get rid of it. Then, once the immune system
has done that, there are memory cells and so those memory cells circulate around, and if they
see other melanoma they’ll get rid of that too.
Are there any downsides to this because isn’t it all noninvasive?
Dr. Daud: The biggest downside we’ve found so far is that the electric shock itself is kind of
unpleasant. It’s a little bit like sticking your finger in an electric socket. You know how you get
that jolt or you touch like a light terminal, a battery, or something like that, that’s how it feels like.
The electric jolt will only last for a few milliseconds. We have done this in a lot of patients and
what almost everybody says is that once the impulse is done you’re back to normal. There’s no
nausea, no vomiting, no hair loss, and very few side-affects following it. However, while you’re
having it done it’s kind of unpleasant and we use medicines to reduce all that discomfort and
pain and also use some local anesthetic to numb the needle. Because the probe has six
needles in it and so that goes into the lesion; so, you kind of feel like something is sticking into
that lesion and we use a local anesthetic so you won’t feel the pain of the needles going in.
However, you do feel that electric jolt. I think that’s the major disadvantage.
Does all melanoma start on top of the skin?
Dr. Daud: Not all, but the majority starts on top of the skin. There are a couple of different types
of melanomas that don’t start on the top of the skin. There’s one kind of melanoma that starts in
the pigment layer of your eye, behind your retina or in your iris. So, that’s known as ocular
melanoma.. Then, there’s a second kind of melanoma that starts in your mucus membranes and
it’s found in your in the nasal cavity, in the nasal mucosa, in the rectum, and vagina. So, that’s a
kind of melanoma that we don’t think is related to sun exposure. It’s related to something else,
we don’t know exactly what it’s related to.
Would this work on some of those types of melanoma as well?
Dr. Daud: I think it could, but we haven’t tested it on mucosa melanoma or on ocular melanoma
partly because they’re unusual and also because you’d have to do it in in that location and so
it’s just a matter of finding somebody who is a suitable candidate and if they are interested in
doing it.
So, are you involved in a second trial with this?
Dr. Daud: Yes.
Tell me a little bit about that and it says that 95 percent of treated lesions showed some
response?
Dr. Daud: Yes, that’s right. So, that has to do with the local efficacy of the treatment. Let’s say if
you have a lesion here or a lesion here you do the electro operation on the lesion, the vast
majority of lesions will regress and either shrink down or just totally disappear. I think that’s
impressive, but I think that’s not as impressive as the fact that you’ll get distant lesions to
respond. The reason I think that is because when you have distant lesions responding that’s
telling you that your immune system is woken up and is on the case. So, if you your cancer
divides and decides to go to some new place, you’ll still have some activity against the cancer.
That is why I feel this is so exciting, the fact that you’re having this kind of vaccine effect almost.
Do you see this as a cure?
Dr. Daud: I think so. I mean it’s a part of a cure. I don’t think in the current form it’s a cure partly
because it only been through Phase I and Phase II testing; so I think there is a long ways to go
before we can say that it’s that good.
Can you tell me a little bit about Martin?
Dr. Daud: He is a gentleman who’s a super active guy. He golfs. He’s an outdoorsy person,
very active, just a wonderful human being. He had melanoma on his leg, close to his ankle. He
had that taken out, had a recurrence there, that was taken out also. Then, what was noticed is
that he started having melanoma spots develop just above his ankle. We know from the history
of melanoma that this type of melanoma, which is called in-transit disease, where you know the
melanoma starts recurring outside of the area where the surgery was done is sometimes a
precursor to wide spread disease. So, if you could stop it at that point that would be wonderful.
That is what we’re hoping to do for him.
If this treatment doesn’t work for him, what are his best options?
Dr. Daud: The other options for him would be surgery, which he’s had a couple of times, but
you can have surgery more times. You could keep on taking more chunks of skin off. The other
option would be systemic treatment like chemotherapy, immunotherapy, or targeted therapy.
Then, the third option would be something known as limb profusion where chemo is infused in
to your limb and it’s a pretty extensive kind of surgery that lasts eight or nine hours.
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