Day 1 more IL2 and Stem Cells   October 7th, 2011

From Linda…

Jake had a rough night. I was thankfully he avoided the rigors after Il2 dose #2 and #3. He developed chills about 1.5 hours after each but a quick wrap-up with heated blankets sent him back to slumber land without more drugs.

While he was sleeping, I skipped out about 9am to grab a shower and breakfast at the Lodge. When I got back with the kids, Jake was awake but looking very weary and drawn. The nurses and doctors were concerned that his lungs were suffering from water retention which was causing labored breathing. They put him on oxygen, took some chest x-rays, and began a close watch on his vitals.

After a careful review, the doctors decided no more IL2 for Jake. Another dose would just worsen his symptoms and land him in the ICU. Although the protocol allows for up to 14 doses (no one makes it that far), the average is 4-6. The doctors were keen to reassure Jake that a strong response to the IL2 means happy active warrior cells, but success is NOT dependent on the number of doses. Those evils rigors on the first dose were a strong response.   The good news is Jake can now start his recovery process.

And even more exciting was the event of the day “Stem Cells”. As you know Jake had Total Body Irradiation (TBI) which wiped out his bone marrow. Today, Jake received back the stem cells collected from his own blood several weeks ago using apherisis. These will repopulate his bone marrow and get his body making blood cells again. This usually takes about 10 days to occur.

I’m spending another night on the fold out bed but we are both looking forward to a little more sleep.

 

I have successfully finished being exposed to 1200cG (centi-grays) of radiation over the course of the past three days thanks to an awesome team of specialists. And I even have a certificate to prove it!

The wonderful certificate of appreciation I received this afternoon after my sixth and final course of full body radiation. Even got a hug from my radiation nurse!

The wonderful certificate of appreciation I received this afternoon after my sixth and final course of full body radiation. Even got a hug from my radiation nurse!

And still, beyond a dry mouth, and a bit of fatigue, not much wear to show for all that, yet. Hopefully the radiation did its job in killing off all my bone marrow – that’s what the main purpose was of getting the radiation.

The oncology radiologist I spoke to this afternoon after my final treatment commented that I went through the radiation treatment amazingly well, and while he doesn’t know exactly why, perhaps my relative youth, good health, and good energy levels might have helped. He also indicated that there is a chance that some of my organs may have been damaged a bit (which would be fixable or heal-able), but only repeated testing (urine and blood samples) will determine if any such situations exist. So far so good (and please continue knocking on wood – it’s definitely been helping.)

On to what’s next…

One of my favorite movie quotes is from the 1980 version The Blues Brothers:

Elwood: It’s a 106 miles to Chicago. We got a full tank of gas, half a pack of cigarettes, it’s dark and we’re wearing sunglasses.
Jake: Hit it!

There is the absurdity of wearing sunglasses at night, but in reality is it a checklist in the pursuit of a goal. In Jake and Elwood’s case, that is to deliver concert proceeds to a tax collectors office in Chicago, while being sought by the police, and an extremist group.

My current version of this movie quote is:

Jake: I’ve just been radiated and chemo’d. It’s five more days until the treatment is over. I have a couple small bags of Haribo gummi bears, a full jug of water, no idea what I am facing and am covered by a fluffy duvet.
Jake (speaking to myself): Hit it!

Okay. Maybe not as memorable, but to me it has the same feeling. And in my case the ultimate goal is NED – No Evidence of Disease.

To get there I need to get through the next five days of treatment with IL-2 in the form Aldesleukin. From what everybody has said, intensive IL-2, which will start to be administered few hours after my TIL cells are administered tomorrow in order to super-charge the TIL cells and help them achieve their cancer-killing task. (But, as a caution, it will not be clear for at least a month how effective they were, and may take many months to verify total shrinkage and disappearance.)

After the first administration of IL-2 I will continue to receive 15-minute infusions via IV every eight hours until my body just cannot handle it anymore (based on physiological responses related to breathing, organ function, and also on mental function). There are a maximum of 14 doses of IL-2 that will be administered, but my nurse has never heard of anyone that has even gotten close. IL-2 comes with fevers, chills, rigor (shaking during chills), and all sorts of other pretty scary things – more details in the fine print available here.

Whenever it is that my IL-2 treatment ends, I will be a bloated wreck for a bit (an IL-2 side effect is the release of stored water in the body being pulled out of its regular places, resulting in a 20-30 pound “bloat” – and yes, I will have someone take pictures of Puff Daddy Jake :-) ). But I’m betting on being a bloated Jake on his way to NED.

And, speaking of photos – I know I have been remiss in providing images with posts lately, so below are several images to captured over the last week:

Linda and the kids move in to my hospital room to keep me company. Here everyone was getting their wifi connections working. Honestly, they really do pay me a lot of attention when I'm not sleeping

Linda and the kids in to my hospital room to keep me company. Here everyone was getting their wifi connections working. Honestly, they really do pay me a lot of attention when I'm not sleeping. We play games, watch movies, talk, and even torture the kids with doing their more traditional forms of schoolwork.

My IV tree the night they were administrating my first dose of Cytoxan to kill my current immune system. Festive!

My IV tree the night they were administrating my first dose of Cytoxan to kill my current immune system. Festive!

 

Cyclophosphomide a.k.a. Cytoxan, close up.

Cyclophosphomide a.k.a. Cytoxan, close up.

Linda and the kids enjoying a take out meal which I got to try part of with doctors' permission. I managed two wings and two fries before I was full.

Linda and the kids enjoying a take out meal which I got to try part of with doctors' permission. I managed two wings, a small chunk of dark meat, and two fries before I was full.

 

Here I am in my hospital room working on this blog post about Day -1, after finishing my final radiation treatment. That's Renaissance Bear next to me.

Here I am in my hospital room working on this blog post about Day -1, after finishing my final radiation treatment. That's Renaissance Bear next to me.

 

 

My neutropenia continues. I’m down to an absolute count of 54 neutrophils per cubic millimeter of blood, and at this rate I without doubt will be down to as close to zero as is humanly possible before my TIL cells get administered on Thursday.

Until then I’ll be getting a whole bunch of full body radiation. I went through my first rounds today – the first around 8am and the next around 2:30pm. A similar schedule will continue tomorrow and Wednesday.

Having also just had my last dose of fludarabine administered about an hour ago, I am now officially done with the application of chemotherapy and am moving on to deal with the side effects.

My energy levels are pretty darn good, and I’ve not had nausea (everyone, please find wood to knock on!). And my sporadic fevers appear to be dissipating.

I have been told that having Linda take me for daily walks around the amazing Hatfield Center I’m in here at NIH has been very helpful for both the energy levels and the fevers, although I have to wander around with a face mask (required because of my neutrapenia) and gloves (additional paranoid measure on my part). However, in that costume people rapidly make way for you if you generate fluid sounding hacking noise. People are pretty funny in how they respond to someone in a face mask.

I have also had some light-headedness today, but I’m told that the Adavan I’ve been told to take before radiation is the cause.

So, all that’s the good news.

Less pleasant effects are appearing however, including intestinal distress (requiring three Imodium-equivalent loperamide tablets, to, um, stem the flow) and bowels which are trying communicate audibly in a language I have yet to parse (I think it’s a dialect of Wookiee).

I have also developed a fair bit of pain at the base of my jaw, on both sides. Makes chewing painful, and the outside of the jaw is rather tender.

And from a continued oral perspective, I now also find myself with salivary glands that don’t really produce any saliva except for some thick mucus, sometimes. So, at times, when I try to eat anything my mouth gets all gummed up. I need to keep moistening and loosening things up in my mouth with lots of liquid – water seems to work best, flavored drinks and carbonated ones the worst). At other time with dry mouth, eating anything without its own liquid (like the protein bar I am masticating now) is like chewing on sawdust. Ugh. And if you don’t hydrate the food in your mouth, you could choke on it. Death by dry cracker. Not a pretty way to go, I’m sure.

The source of these side effects would tend to lean towards the chemotherapy – still messing with my system residually, as the radiation has only just started. None of the doctors have been able to pinpoint the actual source so far, and past consults have indicated that both chemotherapy and radiation can contribute to dry mouth and jaw problems, as well as diarrhea.

It is becoming clear to me that it is not for me to point fingers at a particular treatment component to find blame for the individual side effect, but instead just accept these side-effects as they come along and find the best way to deal with them, and hope they go away soon.

The only thing that appears 99% certain is within two week I will have at least lost the hair on top of my head, but as one of my nurses points out regularly: “Jake – with you nothing is predictable.”

Let me close with a quote out of a fortune cookie Bas got last night: “When you have no choice, mobilize the spirit of courage.” How apropos, eh?

So onward to tomorrow’s unpredictability with the spirit of courage…

 

Our few days earlier this week in the Washington, D.C., area – which were centered on my scheduled testing and interview at the National Institutes of Health’s National Cancer Institute (NCI) – have been dizzying. And shaky, as we got to experience an earthquake during the process. It wasn’t a big deal, but it was interesting to go through and observe, including the mandatory building evacuations.

The Mark O. Hatfield Clinical Research Center at NIH, seen after our evacuation after the earthquake

The Mark O. Hatfield Clinical Research Center at NIH, seen after our evacuation after the earthquake

The actual physical tests and examinations performed this past Tuesday at NCI were routine – taking my blood (13 different vials, though), an EKG, chest X-ray, and a urine sample.

Linda and I also spent time with a social worker who explained how treatment at NCI worked: it’s free to the patients, as it is a federally funded research facility, and they will even take care of transportation costs for the patient (but not the spouse or children of the patient) from anywhere in the U.S., as often as necessary. There’s also a small lodging stipend ($50/day) for the patient’s hotel room if the patient is an outpatient.

One of the benefits, in terms of treatment and medical care, of not having to deal with the costs of such care (personally or via insurance companies) is that there’s no wait or delay in waiting for pre-certifications or considerations about the expense of tests that may or may not produce useful results.

That philosophy became evident on Tuesday afternoon (after the hubbub from the earthquake we experienced had settled down), when the new Fellow (a term for a doctor on a long term rotation) assigned to me suggested I could have surgery in the next couple of days to remove my largest tumor to use in harvesting lymphocytes (immune cells) which would later be used to fight my rapidly spreading and growing melanoma.

The mere suggestion that they wanted to operate on me indicated that my acceptance into the so-called TIL (tumor infiltrating lymphocytes) protocol was almost a given at that point. That was a huge relief.

As part of our meeting with our Fellow, we also met with the Attending doctor who has worked at the NCI immunotherapy clinic for the last decade. Fellows rotate out every year in July, while the Attending doctors rotate every month or so, incidentally. They gave me a physical examination, palpating me to see if they could feel any tumors (and they thought they could feel some around my lymphadenectomy site). They also confirmed that the rapidly growing mole that I had on my right thigh, located about 1.5 inches from the old melanoma mole, was a new melanoma, as I had surmised a couple of weeks ago.

One initial idea raised at this meeting had been that they might try a radical surgery to remove both the large 3cm+ tumor found on the scans last month, as well as any other lymph nodes, in the hopes this might eliminate the cancer from my system, but after the examination and the identification of the mole they agreed that survey was not the way my cancer could be dealt with as I likely had some “melanoma channels” throughout which the cancer had spread and continues to do so. No surprise there – I already knew that instinctively based on how aggressive my melanoma has been.

In order to help determine the best course of action, as well as provide data that was incomplete in my records, I was asked if I could come in the following day for a brain MRI and a CT scan of my abdominal and thigh regions. We had fortunately tacked an extra day and a half to our trip when we planned it, so I was able to stay at NCI all day yesterday (Wednesday) for those two scans, which were arranged for me by a uniformed research nurse who is our direct link with any information or support we need on the medical side.

At the end of the day I exchanged e-mail with our Fellow, and she informed me that the CT scan did confirm that all my tumors were continuing to grow (again, no surprise there), but that from a treatment perspective, this was helpful as it provided more potential samples, as well as reference tumors to use to see if the treatment was working once started. However, surgery was not happening this week, as she and the Attending wanted to present my case formally to their colleagues at the weekly Monday staff meeting, and solicit ideas on how to best proceed with my tumor resection and subsequent treatment.

The clinical protocol, which is really a clinical trial, discussed with everyone on Tuesday has several steps.

First is the harvesting of lymphocytes from a tumor. They need at least a 2cm wide tumor to do this, and my largest tumor is quite a bit larger than that at this point. This is an invasive procedure but in the case of my tumors in the lymph nodes is less tricky than removing a tumor from an organ which thankfully my melanoma hasn’t gone there yet.

Next, the labs at NCI extract the lymphocytes and grow them. They use Interleukin-2 (IL2) to help “boost” the cells as they breed them. This process takes a couple of weeks or so, if it is successful.

Once it is confirmed that the lymphocytes are replicating and growing properly, I would get flown down to NCI to be formally admitted into the clinical trial.

For those of you interested in the details, the link to this trial is here. There is also a really good FAQ here.

In case you also are interested, the rather scientific title of the trial is “Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Tumor Infiltrating Lymphocytes Plus IL-2 Following Non-Myeloablative Lymphocyte Depleting Chemo Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI)”.

Once I signed the agreement to participate in the trial, a computer would flip a virtual coin to randomize me into one of the two arms of the trial. The first arm is the basic TIL treatment, while the second arm is the basic TIL treatment with total body irradiation (TBI), namely three days of extreme radiation treatment. As I understand it, the purpose of the trial is to determine whether or not the radiation component increases the cure rate appreciably or not across a wide range of people. The current belief is that it makes a small difference, but this trial will help quantify that difference. That in turn will help determine whether the amount of difference is significant enough to justify the abuse of the body the radiation treatment adds to the process.

If my virtual coin flip put me into the arm with TBI, I would stay as an inpatient for a week at NCI while they extracted stem cells from me. These stem cells would be grown and stored for reinjection after the radiation treatment was over, since the TBI would kill all the cells in my bone marrow, which include cells which generate all of my white blood cells (for fighting infection, among other things).

This initial visit would be shortly followed by another visit to actually perform the core part of the treatment.

First step in the treatment would be to have five days of chemotherapy to kill my immune system and create a vacuum to allow my boosted lymphocytes to both have a more dramatic effect on my melanoma tumors (as well as individual bits of melanoma floating in my system) as well as prevent my body from just reabsorbing the injected lymphocytes without letting them perform their intended function. Note that the chemotherapy would be unlikely to have any effect on the metastatic melanoma in my system.

The chemotherapy side effects would be much the same as for traditional cancer chemotherapy, including full body hair loss, nausea, fatigue, etc.

If I were in the TBI arm of the trial, the chemotherapy would be immediately followed by the full body radiation, which has a pretty nasty set of side effects, some of which overlap with those from the chemotherapy. The radiation side effects can (and likely will) last many months, or even the rest of my life (including infertility – fortunately not something I am concerned with at this point in my life). The radiation would further weaken my immune system in order to make my reintroduced lymphocytes more effective.

Once my immune system was wiped out, the lymphocytes would be administered via an IV, and if I were in the TBI arm, the harvested stem cells would be administered as well to help my bone marrow regenerate to rebuild my immune system.

I would then go on a short course of intensive IL-2 (up to 15 doses, given eight hours apart) to further boost the lymphocytes now in my body, to help them better battle my cancer cells. After that it would be just a matter of time to recover from the nearly two week abuse of my body in order to try and cure the cancer.

The amount of time for recovery from the highly weakened state depends greatly on a number of factors, but the trial documents suggest for the non-TBI arm it should be two to three weeks in the hospital. For the TBI arm, it would be that plus four to six months of recovery to overcome the recurring fatigue, nausea, and other side effects that will undoubtedly arise.

There would also be return visits back to NCI every four to six weeks for scans to see how effective the treatment was. That would go on for a year, with semi-annual visits after that.

The one thing that this arduous treatment offers that so far we had not heard is the possibility of a near total cure. Statistically this has occurred in approximately 50% of the subjects, but that’s a heck of a lot better than the odds with traditional adjuvant treatment for melanoma, which in most cases, if it works, only seems to put off a subsequent recurrence to a later date (albeit potentially a much later date). And that difference – between a cure and a delay – is what will make this TIL treatment – with or without TIB – worth all the sacrifices necessary to get through the treatment.

In closing, I would like to also give special thanks to my new friend Jamie. Jamie blogs as Melanoma Mom (http://melanomamom.blogspot.com) and has been getting treatment at NCI since March for metastatic melanoma (read her blog for details). She and her husband Jeff are incredibly well-informed about various trials and protocols at NCI, as well as the logistical issues of being an in-patient at NCI. And Jamie is taking part in a rather revolutionary treatment herself starting in about two weeks at NCI. She, Jeff, and their beautiful baby boy, Kai, were kind enough to get together with us on Tuesday night (they live only 20 minutes from NCI). We learned so much from her and Jeff, and are thankful to number them among our friends now.

One simple thing Jamie taught us that I can easily share with you is a toast when you share a drink with others: “To NED!”

NED is an acronym for “No Evidence of Disease”, and that’s Jamie’s goal and my goal for our respective melanomas.

So please hoist your glasses to NED, often and with gusto! I know I certainly will!

My next post will be once my treatment course and schedule solidify just a bit, hopefully early next week.