Day -6 Towards TIL For My Melanoma   September 30th, 2011

Day -6 Towards TIL

I guess no one made clear to me that I was supposed to be suffering from nausea the morning after my first dose of Cytoxan. When I greeted the doctors on rounds this morning all cheery and upbeat they wondered if it had been administered. Apparently my lack of nausea is something of an anomaly – I prefer to think of it as me being special.

The last 24 hours have been spent peeing and peeing and peeing. I think I’m pretty close to 12 liters of urine output at this point, and I still have another 23.5 hours to go of urine madness. I am required to pee into a “urinal” (not the men’s room kind) – it’s a plastic jug with a handle, and it’s got measures on the side so that the nurses can verify I am meeting my minimum quota of 312 mL per two hour measurement period. I have far exceeded that. In fact, one of my nurses has commented that if I were one of the X-Men super heroes, I would undoubtedly be known as “The Urinator”. Beware his toxic yellow streams!

The issue with peeing this frequently (at times every 15 minutes due to the application of a drug called Lasix (also known as Furosemide) is that you don’t get much sleep, so my biggest side effect from the first 24 hours of my condensed chemotherapy is being really tired. I also had a headache and a small fever which both seem to have gone away after the application of Tylenol.

Linda and the kids kept me company for most of the day, which was very comforting.

As I write this, I’m getting my second dose of Cytoxan. I’m knocking on wood and hoping that nausea and diarrhea don’t follow since I’ve avoided them so far.

I’ve managed to catch a half hour of sleep here and there and that’s helped. Knowing I only have another 23.5 hours of pee madness ahead of me provides me a goal to work towards. And tomorrow night I get untethered from my IV after my dose of Fludarabine, so I can have a night of unencumbered sleep.

 

The Start   September 29th, 2011

From Linda…

The day began early at 8am with a CT scan to measure and check the growth of his tumors. At this point, they told us that the target start time for chemo would be 4pm.

The powers that be decided a MRI would be a good followup to get a more exact measure and Jake was on call for a time slot. About 2pm we got the COA or Certificate of Approval that Jake T cells in the lab were a 100% go for the start. Yeah! Woohoo! Yippee! This meant that the pharmacy could start making Jake’s personal chemo cocktail.

Jake arrived for his MRI at 3pm to be told it had broken down, but they got it up and running to get him in by 4pm and out about 5pm. Finally, we were just waiting for the chemo.  At 7:30pm, Jake officially began the chemotherapy portion of his treatment. Treatment has begun!

A toast to N.E.D.

and a mantra from the chaplain

 

All will be well
And
All will be well
And
All manner of things
Will be well

 

Chemotherapy Starts Tomorrow   September 28th, 2011

Today ended up being a quiet day that I managed to spend almost entirely with Linda and my children. Due to the on-going growth of my tumors in at least my right thigh (I have several that are now palpable (feelable), but were not two weeks ago), I was scheduled for a new CT scan to provide a better reference point for the post-treatment CT scan.

I’m pleased by the idea of getting a reference scan right before treatment because it will show more clearly how much tumor shrinkage has occurred due to treatment when compared to my first post-treatment scan in month and a half or so. If the scan from two weeks ago were to be used for this comparison, the tumor shrinkage amount would be skewed by the intervening new growth, and I would have to wait for the second post-treatment scan for more accurate results.

Anyhow, they ended up not having an available slot for a scan today, so I’ll be doing that early tomorrow morning instead, hence some extra hours with the family, in which we ran some necessary errands and enjoyed a nice meal out together – the last one for quite some weeks.

My treatment schedule in chart form - Day -7 is Thursday, Sept. 29, 2011

My treatment schedule in chart form - Day -7 is Thursday, Sept. 29, 2011

Tonight at 1am I start getting hydrated by IV in preparation for the start of my chemotherapy tomorrow.

During the day tomorrow I will receive my first of two doses of Cyclophosphamide (Cytoxan), a toxic chemical designed to  stop cell growth. It is toxic enough, I understand, that the nurses who bring in the one hour IV drip bag do so in a haz-mat suit to avoid exposure (since they have to administer the drug frequently). I hope to remember to take a picture of that.

I will get a second dose of Cytoxan on Friday. I will also start a five day course of Fludarabine tomorrow.

During the first three days of the chemotherapy I will be required to urinate (pee, piddle, wee wee, wizz, tinkle, etc.) every two hours, around the clock, in order to prevent Cytoxan-tainted urine from sitting in my bladder for long periods of time and causing bladder damage, and will also receive Mesna, a medicine intended to prevent the bladder from being irritated by such frequent use.

I understand, in addition to the other side effects from the drug (including major nausea), that being constantly woken up and urged to pee is one of the most exhausting parts of the treatment (the other being the IL-2 which comes at the end). Fortunately, I’m a peeing machine, so I should be up to the challenge. I should add that I will be heavily hydrated to ensure there’s enough liquid in my body to produce results every two hours.

I am guessing, based on what I’ve heard and read (and related above), Linda will be posting updates here instead of me until I’ve been off the Cytoxan for at least a couple of days.

Most patients appear to better deal with the Fludarabine which continues to be given for three days after the Cytoxan.

We’ll see.

 

Tuesday: Starting with a restless and mostly sleepless night, I arrived in Bethesda around the middle of the day, and checked in my room in the 3NW immunotherapy wing of the Hatfield Building, greeting all the fabulous nurses I have come to know from my prior stay. After unpacking, I had a chest X-Ray, an EKG, and blood work done. All look good!

My platelets, which had dropped to a level of 30 last week were up to a healthy 130, which resulted in a high five with the doctor as we celebrated, albeit breifly, that my blood counts were good enough to allow for the protocol to proceed unimpeded.

Linda and kids were here by late afternoon and settled into the adjacent Safra Lodge, which is quite a nice place. The Lodge is on the NIH campus, same as NCI, and has great facilities for families whose loved ones are being treated only a few hundred yards away. The rooms themselves are like regular hotel rooms, but there’s a huge shared kitchen area for the storage of food, cooking supplies, and leftovers, and there are a number of nooks which provide quiet space for stressed out family members, and in our case places our kids can work on school stuff.

Best of all, the Lodge is free – which is important in an area where the average hotel room night tends to run around $250/night. As one might imagine, the Lodge is quite heavily booked – up to two weeks in advance, so Linda and the kids will need to move to a regular hotel on October 2nd for four nights before moving back to the Lodge, unless those dates happen to free up for them. They are back until at least October 20th, my projected departure date.

I had expected Wednesday to be the start of chemotherapy, but that appears to be actually Thursday.

Instead, Wednesday provides a buffer day in case there’s a need for additional scans or labs, which will be determined after rounds in the morning.

We will have more details on the actual treatment process later today, probably.

Also, Linda has been set up with an account on this blog, and may post in my stead should I be feeling unwell enough to post on my own.

 

If you have a short attention span, here’s the big news: My Tumor Infiltrating Lymphocyte (TIL) with Total Body Irradiation (TBI) treatment starts next week, on Tuesday, September 27th.

The long version, including historical information, follows below.

My week at the National Cancer Institute (NCI) has gone quickly, but not without some complications.

On Wednesday, I got my scheduled stem cell apheresis, this time through my newly installed Hickman catheter. It was wonderful to not have to get stabbed again with needles for this process, especially as the bruising I incurred last week for the feeder apheresis are in full bloom with all sorts of color.

But the stem cell apheresis on Wednesday was pretty tiring too. As I later found out, part of this was because the process caused my magnesium, potassium, and platelet counts to drop significantly. Contributing to this was that this apheresis also required that 30 liters of my blood (about five time the blood supply in my entire body) to be fed through the centrifuge over a six hour period.

I spent the rest of the day resting and dealing with a related headache, under the assumption that all had gone well with the stem cell apheresis. However, at midnight, deep into Ambien-assisted slumber, I got woken up and was informed that they did not manage to collect enough stem cells (the minimum required by the protocol is 4 million, but 5 million is more ideal), and that I would need to go through the process again on Thursday morning. No further details were available, but I was given another pair of Filgrastim shots, and put on an IV with potassium chloride to help boost my electrolytes (and potassium levels).

So, yesterday morning I found myself in the apheresis center again, for another 30 liters of blood processing. Turns out that the first day produced 2.6 million stem cells, so not a complete failure. Fortunately, yesterday’s collection produced another 2.04 million stem cells, for a total of 4.64 million cells, sufficient not to require additional vampiration (and delay treatment). Because of the unexpected second day of apheresis, I also had to rearrange appointments with doctors from radiation oncology and from the dental clinic. In each case the doctors advised me on the side effects of the radiation treatment (which are potentially significant). But other then sterility and an increased chance of early cataracts, only these effects are generally transient (but could last for many miserable months).

I fortunately had also learned first hand about this from a couple where the husband had finished treatment about two months ago – they learned about be from Melanoma Mom Jamie’s blog, and were wonderful enough to look me up at NCI to see if they could help with any questions I had about the process. Thank you so much Pam and Joe!
In any case, the anecdotal evidence suggests that the aftermath of TBI is well worth it in terms of increased probability of response to the treatment. The amount of response benefit is actually what this clinical trial is designed to help define.

Yesterday, I was also told that I had excellent teeth and dental health. I think that was the high point of my day. The day ended with more potassium infusions, and six units of platelets, both of which helped my blood counts creep towards normality.

I wrapped up my stay this morning with a simulation scan to prepare for my full body radiation treatment (which goes on twice a day for three days, starting October 3rd).

The end result was that I now have a bunch of lines on me, drawn with a permanent marker (fortunately not really permanent), with the critical markings covered by waterproof tape. The lines will be used to align my body with respect to the photonic radiation emission equipment. By the time I’m done with the three days of radiation, my body will have absorbed 12 Grays of radiation, and my lungs only 6 Grays. The Gray is a unit of measure that relates to “rads”. It is a significant dose for full body exposure, but small compared to localized radiation.

As I already indicated in the abbreviated version of this blog above, I learned that I have been scheduled to return to Bethesda on Tuesday, September 27th – so a mere four days from now. The first day will be spent getting me all set up, and I start my five day course of chemotherapy on the next day, followed immediately by the three days of radiation.

Again, the whole purpose of these two components of the overall treatment is to kill my immune system as well as the cell generation in my bone marrow. The idea is that the resulting environment (no immune system) gives the TIL the best possible chance to do its thing – namely kill all those nasty melanoma cancer cells that are still intent on spreading throughout my body, without interference from my own normal immune system.

After the TIL cells are administered, the stem cells will be administered, then I get the mind numbing IL-2 treatment to boost the power of my TIL and stem cells, and then there’s recovery…

I will stay at NCI until it is deemed safe for me to be exposed to much of the world, namely when my immune system has recovered enough to ensure that I will no longer be in danger of infection from the most minor germ. Right now, my return date to Boston, as a bald, easily nauseated, and very tired person, is scheduled to be October 20th, but that date is subject to change based on my recovery, and the on-going entropy that is part of my life these days.

I want to extend a very special thanks to Jamie and Jeff for letting me be part of their nightly take-out dinners during my stay at NCI. Thank you both for your friendship and hospitality.

The few days I have in Boston (I am en route now) are going to be spent with family. In fact, my parents flew in from the Czech Republic yesterday – the original plan being that we’d be spending a couple weeks together. However, the melanoma train stops for no one, so we’re down to only a few days together. But that’s okay, because my train’s destination is NED – No Evidence of Disease. And a pig roast at our house in Bonaire in the spring!

Note: I want to mention to those folks who have been depending on e-mails from me for notification of new blog entries, I will no longer be sending out those e-mails during treatment. And I will not be posting notification on Facebook or Google+ either. My upcoming posts, throughout treatment, if I can manage them, will be a lot more succinct than my usual posts, and to see them you will have to remember to check back here at http://www.jakestake.tv every so often to see what’s new.

 

Poignant Quote by Tim Russert   September 18th, 2011

I was exploring the fabulous news and media museum called the “Newseum” in Washington, D.C. yesterday.

One of the exhibits there is the office of Tim Russert, a news personality who died a few years ago at the tender age of 58. And one of the items there was a Starbucks coffee cup inscribed with the following words of wisdom from Russert:

“You can shower a child with presents or money, but what do they really mean, compared to the most valuable gift of all – your time? Vacations and special events are nice, but so often the best moments are spontaneous ones. Being there. Every moment you spend with your child could be the one that really matters.”

— Tim Russert, former host of NBC’s Meet the Press and author of Wisdom of our Fathers.

Beautifully said.

 

I write to you tonight from my private (for now) room at the National Cancer Institute (NCI) in Bethesda, Maryland. For those of you who follow this blog closely, you will understand that this means that when I signed the agreement to participate in the Melanoma TIL (Tumor Invading Lymphocytes) clinical trial here yesterday, I was randomized into the arm of the trial which adds Total Body Irradiation (TBI) to the base TIL treatment.

This is actually a good thing – even with the nasty side effects – because the use of TBI, based on anecdotal evidence, appears to contribute handily to improving the response to the TIL treatment. And, as it was confirmed this morning that the melanoma has now started to spread to my liver and my lungs (small tumors were spotted on the CT scan on Wednesday), I am pushing for every bit of help the TIL treatment can get in killing my melanoma. So TBI is most welcome as a part of my treatment.

The emblem of the surgical unit of the National Cancer Institute

The emblem of the surgical unit of the National Cancer Institute

A short while ago I received my first set of injections of a medication called G-CSF a.k.a. filgrastim a.k.a. Neupogen. The purpose of this medication is to stimulate the growth and release of stem cells into the bloodstream. The careful readers among you may notice that I referred to “injections” in the plural. As it turns out they can only inject a maximum of 2mL of filgrastim per injection site, and my dose is 2.8mL, so they split the dose in two, shot into opposite sides of my belly. I apparently will be getting two shots every 12 hours (at 7am and 7pm), instead of one larger one, for the next five days. Eek.

I guess I shouldn’t be surprised by having to be poked twice as often, as needles have been a big part of my week here in Bethesda. In counting the number of times I have been punctured in the last three days, I get to twelve. Only nine of those were successful. This includes the two belly injections tonight, two sets of drawn blood, three IVs, and two related to my leukapheresis. The puncture wounds on my arms alone make me look like a junky. But that should have changed with the small surgery I had this afternoon to install a double-lumen Hickman catheter (more on that later).

The feeder apheresis, also know as a leukapheresis, was pretty interesting. As described in my prior blog post, the idea was to remove blood flowing through one arm, filter it for the desired blood component, and put the remaining blood components back into my body in the other arm. And that’s pretty much how it worked yesterday morning. All in all, 15 liters of my blood (which is about 3-4 times my total blood volume) was run through the apheresis machine to produce almost a liter of mostly white blood cells. The process ran nearly four hours, and after the initial installations of the intake and outtake needles, was pretty painless.

My white blood cells after the leukapheresis

My white blood cells after the leukapheresis

The filtering process is actually a centrifuge which forces the components of my blood into separate layers, one of which is the white blood cell layer. It’s next to the red blood cell layer, which is why the above bag of white blood cells is reddish in color. The white blood cells will be further separated out in a lab, and then fed to the TIL cells being grown for me, since those cells will appreciate a “homey” environment (namely from my body).

Next Wednesday morning, all the stem cells being released into my body will be collected via a stem cell apheresis, but this time I won’t need to be punctured again. That’s because this afternoon I had a dual-lumen (two port) Hickman catheter installed into my jugular vein.

Diagram of a dual-lumen Hickman catheter

Diagram of a dual-lumen Hickman catheter

The doctor installing the catheter indicated it was 23cm (almost 10 inches) long. It starts in the middle right part of my chest, loops up over my right clavicle, and down again into the vein. At the end of the catheter (the part inside my body) are two openings about 1.5 cm apart, at right angles from each other. The catheter itself has two independent channels (lumen), one connected to each of the openings.

On the end of the catheter sticking out of my body are two ports which can take IVs, but more importantly, can also be used for my stem cell apheresis so I don’t have to be poked again for that (or future apheresis or any IVs other than for CT or MRI contrast injections).

The catheter is pretty uncomfortable tonight – a little bit of pain, plus a feeling like I bruised my neck muscle, but the doctor (and the nurses here) said I would get used to it in a couple of days. Good thing, since I need to continue to keep it in for at least three months.

I also had a dietician come visit me today to discuss my dietary needs and restrictions once I start my actual treatment of chemotherapy followed by the radiation and IL-2. And, even more importantly, the months after treatment where I will be recovering from the effects of the radiation. About half-way through my treatment, I will achieve a point where I am “neutropenic” – having little or no white blood cells with which to fight off any infections or illness, and that will require being extremely careful about what foods I eat (and whose hands I shake).

However, even as my white blood cells come back after the reintroduction of my stem cells, I’ve been told that I will need to maintain a neutropenic diet for about three months after treatment to avoid complications. This cuts a lot of fun and interesting food out of consideration for consumption, so perhaps I should take solace in the fact that I won’t have much of an appetite, as well reduced taste sensation, during my recovery.

An overview of the “can and cannot eat” items in a neutropenic diet can be found here.

After I return back to Boston on Friday or Saturday, I can only count on being there for between five and twelve days, and I’m betting on the lower end of that range based on how fast things have gone at NCI. Then I’ll be back in Bethesda, starting my treatment, and hopefully moving my way through the final step towards NED – No Evidence of Disease!

 

Life is like a whirlwind, at least mine is right now. You get swept up when you’re not exactly expecting it, and you hope you get put down safely and soon.

My previous blog post left things hanging a bit, and I apologize for that. Those of you who get e-mail notifications from me already know, but I got a call last Wednesday afternoon that my cells were already ready. That was just one week after the tumors used to grow those cells were surgically removed from my body. Needless to say, we were stunned by both the good news and the speed with which it arrived (picture mental and physical “happy dances”).

With my surgery wounds pretty much healed now, I am scheduled to depart for Bethesda again tomorrow, and while at the National Cancer Institute (NCI) on Wednesday, I will repeat all the scans and tests I had done in late August – all because those tests fell one day outside the three week window prior to signing onto the protocol. The tests being run include blood tests, an EKG, a chest X-ray, a brain MRI, and a nearly complete CT scan. The next morning I spend about three to four hours getting a “feeder apheresis”, where blood will be extracted from me on one side of my body, materials filtered out to help further feed my grown immune cells (hence “feeder”), and what’s left being put back in on the other side of my body.

The protocol signing (called a “consent”) takes place on Thursday afternoon, at which point some computer is going to determine, randomly, whether my Tumor Infiltrating Lymphocyte (TIL) treatment will include intense total body irradiation (TBI) or not.

If I get randomized into the TBI arm of the protocol, I will be checked in as an in-patient the NCI clinic on Thursday night (while Linda flies back to Boston), and stay there for eight days. Starting at 7pm on Friday, I would get an injection of a drug to boost my stem cell production, and this would continue for the next seven days, twice daily, at 7am and 7pm. During that subsequent week I would also meet with the radiologist, a dentist (because the radiation might impact my dental health), and other specialists. On the following Friday I would go through a stem cell apheresis, to remove a large amount of stem cells in my blood stream. Those would be used later in the treatment to regenerate all my bone marrow cells, all of which the radiation treatment would kill.

Once I leave Bethesda, either this coming Thursday night or at the end of the following week, I will only be in Boston a week or so before returning to NCI to finally start my actual treatment. A description of how that treatment would start is in the blog of my friend, and my hero, Jamie (Melanoma Mom), who is undergoing the same chemotherapy right now that I will soon be going through myself. Jamie isn’t having total body radiation, but is going through a very similar treatment otherwise. Jamie – be strong! We love you and will see you in a couple of days!

Background of TIL
One of the things that kept me off-line quite a bit last week was reading a book that the research nurse for my protocol had recommended. Written about 20 years ago, “The Transformed Cell”, by Dr. Steven Rosenberg, provides an in-depth view of how immunotherapy as a cancer treatment got its launch at NCI. Dr. Rosenberg is “the man” in the world of immunotherapy, as well as the principal investigator in the clinical research study that I am participating in (and I was fortunate enough to meet him the morning after my surgery, albeit briefly).

What fascinated me about the book was Dr. Rosenberg’s detailed explanation about his motivations and his experiments in trying to show that immunotherapy could in fact work to eradicate cancer in a patient. One of the many procedures he helped developed is the transduction of lymphocytes, or in simpler terms, programming white blood cells using gene splicing.

Rosenberg is very forthright about his failures in his book, and the emotional burden of finding himself unable to help many of his initial patients – yet knowing that he was very close to a solution. His book ends (and since this is historical, I’m not giving a lot away) with the cure of a woman using T-lymphocytes which had a gene for TNF (Tumor Necrosis Factor) transduced (injected) into them to make them even better at killing the particular cancer cells the lymphocytes were targeting.

Now, keep in mind, this was 20 years ago. The techniques developed in NCI’s labs then have led to on-going evolution and revolution in immunotherapy around the world, and from all that I have read, Dr. Rosenberg and his team continue to push the envelope. I was pleased to have my new dermatologist in Boston (who specializes in “pigmented lesions”, including melanoma) tell me that Dr. Rosenberg is the Father of Immunotherapy. I am quite sure I couldn’t be in better hands than his, and am very happy I got into his clinical study.

And I’m also excited about my visit to NCI this week, because I’ve been offered a visit and tour of the lab where they grow the cells for TIL (including mine). Apparently this is something offered to every patient, but I’m looking forward to geeking out a bit in my discussions with the lab technicians and specialists.

Other Tumor Factoids
I neglected to mention in my last blog post that during my stay at NCI, I learned a couple of interesting things about cancers from the doctors and nurses there that some of you might be interested in:

– Cancer tumors tend to be quite firm and solid, although that’s not always the case. For some reason I had a perception of tumors being soft and squishy most of the time. However, since they are generally quite firm it explains why doctors will palpate your lymph node regions and abdomen to see if they can feel any solid masses.

– Cancer tumors can be variously colors, although apparently black or dark are more common colorations for tumors.

– There are over 200 different types of cancers, each treated in its own particular way.

Enjoying Life’s Moments
As the above might indicate, I have no idea what my actual schedule is going to be beyond Thursday, until I’ve been randomized. I have already bemoaned the loss of control I feel in terms of planning – something that is really tough on anal retentive and control freaks, like myself. Some of you may recall the Robin Williams movie, “Dead Poet’s Society”, where he taught his students to seize the day (“carpe diem” in Latin). Well, I have been trying to adjust to my lack of control as best I can, and my Latin mottos now include “carpe opportunitas” (seizing opportunities and advantages) and “carpe momentum” (seizing the moment).

One such moment seized was yesterday, as we finally had wonderful weather in the Boston area again, and had learned last week that the annual King Richard’s Renaissance Faire was being held south of us. We set forth to enjoy some hours at the Faire, with one of the major goals being the devouring of large turkey legs. We accomplished that mission handily.

A rare shot - Krystyana, Linda, and Bas all together. Here, getting ready to eat the fare at the Faire.

A rare shot - Krystyana, Linda, and Bas all together. Here, getting ready to eat the fare at the Faire.

Enjoying a massive smoked turkey leg at King Richard's Faire

Enjoying a massive smoked turkey leg at King Richard's Faire

Much to Bas’ consternation, I bought myself a pair of giant butterfly wings which I wore throughout the entire Faire to entertain myself and others with. Bas was convinced my sole purpose in wearing said wings was to embarrass him (he remains firm in this belief, even after numerous explanations to the contrary). At a Renaissance Fair, being partly dressed as a mythical fairy raised nary an eyebrow though. Now, if I wore the wings to Whole Foods or Quincy Market with Bas in tow, that would be a different matter entirely.

Be that as it may, it was a very nice way to spend the better part of a day with my loved ones, and my wings lifted me even higher.

Me with my butterfly wings at King Richard's Faire

Me with my butterfly wings at King Richard's Faire