Ruminations 4: Pet Results, Decisions and Uncertainties

Ruminations 4: PET Results, Decisions, & Uncertainties

April 13, 2007

 

It has been an interesting few weeks, full of
uncertainty, and while some decisions have been made,
the uncertainty will continue for several more weeks.
This is just an interim report.

 

Based on the considerations in the previous
Rumination, we decided to postpone the decision on
radiation therapy until the results of a PET scan on
Tuesday, April 3rd, were back. They did hand me a CD
of the PET (but because of a miscommunication not the
accompanying CT) while I was there.  I looked at the
scan, first by myself and on Friday together with Dr.
McAnaw in Hyannis, and it appeared that there was a
hot spot in the liver, but without the CT we could not
be sure.  On Monday, a complete CD arrived in the mail
and there was no longer a question - there was an
approximately 1 inch hot spot in the liver.  I met
with Dr. Hodi, the oncologist at Dana-Farber on
Wednesday (11th) and we agreed that it was highly
likely (that's as far as one can go without a liver
biopsy, which is not without its own considerable
risks) since there was only a faint hint of the spot
on the PET scan in December.

 

This finding, although not good news, does simplify
the decision making.  There is little point in
irradiating the neck when the liver is a more
immediate threat. Nor is there any point in doing
anything drastic with the liver - while removing the
malignancy surgically is a potential option, there is
little point in doing so since the melanoma cells are
circulating in my blood stream and will, in relatively
short time settle elsewhere, with or without the
surgery. Left to its own devices, the liver will fail
in an average of a year, with a very large standard
deviation, so anything from a couple of months to
several years being reasonable.

 

Clearly, the only meaningful intervention is systemic,
one that will address the metastases wherever they may
occur.  The only FDA approved systemic treatment for
melanoma is Interleukin, which has so many toxic side
effects that most people cannot tolerate the treatment
and stop it before a year is out; it is also not very
effective. There are, you will probably be surprised
to learn, about 168 different experimental studies of
melanoma drugs currently being conducted around the
world. How to choose one for me? Well, first of all,
almost all these studies address cutaneous melanoma
(CM) which is genetically different from the mucosal
melanoma (MM) which I have and which has an incidence
of about 400 cases a year in the US . (number from Dr.
Hodi, see also R.J. Patrick, et al., Primary Mucosal
Melanoma, J. AM. Acad. Dermatol, 10.1016; published on
line March 2, 2007 doi:10.1016/ j.jaad.2006.06.017).
Since the genetic pattern and hence gene expression of
CM and MM are different (Cutin et al., Distinct Sets
of Genetic Alterations in Melanoma, NRJM 353:2135
(2005)) with CM usually expressing BRAF (a gene
controlling another kinase) while MM are much more
likely to express c-kit (a tyrosine kinase).
Consequently, most of these trial drugs would probably
not work on MM. (They only work 10% - 20% of the time
on CM. This is not surprising since there are multiple
pathways and these new drugs each suppress/inhibit
only one.  I was 'pleased' to see my thoughts along
those lines confirmed this week by G.P. Gupta et al.,
Mediators of Vascular Remodeling Co-opted for
Sequential Steps in Lung Metastisis, Nature
446:765-770 12 April 2007 ).

 

That leaves only two possible relevant trials:

 

1) A mouse gp100 plasmid DNA vaccine developed by J.
Wolchok at Sloane-Kettering on a canine model of what
appears to be mucosal melanoma [P.J. Bergman et al.,
Development of a xenogenic DNA Vaccine Program for
Canine malignant Melanoma at the Animal Medical
Center, Vaccine 24:4582-4585 (2006) and J.D. Wolchok &
Y.M. Singer, Current Topics in melanoma, Curr. Opin.
Oncol. 19: 116-120 (2007)] (Dogs develop melanoma in
their mouth or foot pads, which I would think are the
animal model of MM and acral melanoma, respectively.)

 

2) A trial of Imatinib (also known as Glivec) which
specifically targets c-kit, being run at Dana-Farber
by Dr. Hodi.  Dr. Hodi thinks that there is about a
30% chance of Glivec working, and while there is the
potential for unpleasant side effects, they are
reversible by discontinuing the drug.

 

There really is no good basis for choosing between
these two, but since I am already a patient of Dr.
Hodi and since the protocol at Sloan-Kettering would
require a number of several day stays in NY, I have
elected to go (first) with the local protocol.  The
first step is to determine whether my MM indeed does
utilize the c-kit pathway, which will take about three
weeks.  (Discussion of alternatives can await the
outcome of that test.) In the meantime, I will have an
MRI of the brain on the 17th to check for brain
metastases.

 

So, the uncertainty continues for at least a few more
weeks.

 

Meanwhile, back at the ranch, we are happy to report
that our favorite restaurant in Boston has gotten even
better.  They have not only expanded to a second floor
of seating but also expanded their menu.  We ate there
Wednesday evening and were surprised and delighted at
the new dishes.  We tried two, a sushi roll with king
crab and eel, presented as a Godzilla-like snake and a
tripe & menudo soup. Both were outstanding and the
quality of their kim chee (which has always been
superb and much better than anything in the stores)
retains its prize winning position. Korean-Japanese
fusion at Suishaya Restaurant, corner of Tyler and
Beach in Boston 's Chinatown .

 

As soon as we can gauge that Tom's reaction to the
Glivec will be mild, we are planning to go to Italy
for 10 days, mainly to Le Marches , hopefully in late
May, early June. We hope it comes to pass - we are
really looking forward to it.

 

Cheers,

 

Tom.

tags: melanoma