Friday, March 28, 2014

Jane/NF Update:
The last month and a half has been a whirlwind—so much has happened since my last post.  Will start with a day-to-day accounting of the first couple of weeks:

At the time of my last post we had just received the final results of Jane’s most recent MRI and learned that her tumor had continued to grow while on Gleevec this past year.
Plot of the volume of Jane’s tumor over time.  (Note:  Every data point represents an MRI.  It doesn’t include the three MRIs Jane had before she started medication for her tumor, nor does it include two more she had while being evaluated for a possible stroke at age 4.)
 As of February 19th the available options were:
  1. Continue Gleevec.  The slope of Jane’s tumor growth appears to flatten a bit in the second six months of the trial, but it was unclear to Jane’s doctors whether this truly indicated a small response, or if it was just within the margin of error of the test.  One option was to stay on Gleevec given that, in some children, Gleevec has taken longer to have an effect.  Jane had so few side effects on Gleevec—it was so nice being on such a medicine this past year...  Guess it was too much to hope for that it would actually help, too :(
  2. Join a pilot study with a new drug called Sutent, a drug currently used for some kidney and stomach cancers.  The side effect profile for this drug seemed onerous.
  3. Join a Phase I trial of a new drug, AZD6244, also known as selumetinib.  We have always preferred not to participate in a Phase I trial unless absolutely necessary.  Phase I is testing to determine what is the highest tolerable dose of a medicine (to determine the “toxic” dose).  Once the tolerable dose is established, a drug can move to Phase II when it is tested to see if it is actually effective.  However, this particular medicine would not likely enter Phase II until later this year.

At that time Todd and I decided to continue Gleevec for another six months in the hope that the previous six months indicated stabilization.  Then we began waiting for insurance approval for Gleevec—since we’d no longer be part of a study we would have to get the medicine through a regular pharmacy.  It costs over $1400 a week.

~ ~ ~

A few days later I spoke to one of the doctors involved in the Phase I trial of ADZ6244.  Dr. Brigitte Widemann had been Jane’s doctor when she was treated with interferon alpha-2b from 2010-2012 at the National Institutes of Health, and I have continued to consult with her even after we finished that trial because I trust her so!  Dr. Widemann shared with me her preliminary results with ADZ6244:  out of 17 children who have been on the medication until the 1st follow-up MRI (5 months), ALL had a reduction in plexiform neurofibroma tumor volume.  If Jane joined this trial, she would be the final enrollee in Phase I, and as luck would have it, she would start at the same dose as was planned for the upcoming Phase II trial.  In effect, it would be like starting Phase II, but with just a few more blood tests.

The protocol for the Phase I trial would be:
--Baseline visit for echocardiogram (because one of the rarer possible side effects, heart failure), EKG, blood work, eye exam (because of the risk of problems with the cornea and retina!) and MRI.  We could use the MRI data from the study Jane had done in Indiana earlier in the month, as long as we enrolled at NIH within one month of the MRI date.  That gave us until March 3rd to get all the other testing done—less than a week away!
--Return after 4 weeks for blood work.
--Return after 12 weeks for blood work, echo, EKG, eye exam again.
--Return after 20 weeks for above plus MRI.
In between we'd see our own pediatrician for blood work every 2 weeks for the first 3 months, then monthly until 5 months.  OMG.

The next day, February 24th, we decided to go for it.  It meant Jane missing more days of school and me rearranging a full office schedule, but the potential benefit seemed great.  I get chills every time I think about the possibility of Jane’s tumor shrinking—but then I freak out when I remember that she will only be the 24th child to ever take this medicine…  It is terrifying to read the possible side effects, but we are hoping for the best.

Amidst all of this last-minute decision making poor Helen was home sick with a stomach bug, and I had Jane at an ophthalmology appointment—we still didn’t have an answer for her eye turning inward.  The ophthalmologist didn’t have an answer that day, either, and referred us for an appointment with a pediatric neuro-ophthalmologist.  (Can you say super sub-specialist?)

~ ~ ~

Two days later Jane and I were back in Bethesda, MD at the NIH to enroll with Dr. Widemann.

One lovely feature of NIH is the Children’s Inn (, a residence for patients and their families to stay while receiving treatment at NIH.  It has kid-friendly everything:  playrooms, living rooms, a playground, a fireplace, a library, an arts and crafts room, a garden, and a therapy dog.  Each child also has a mailbox into which every night is delivered a special treasure (usually something like stickers, cards, coloring pages, crayons, or small toys).  The previous occupants of our room must not have checked their mailbox regularly, because when Jane opened hers there was at least a week’s worth of treasures inside.  Jane gasped, “They must have really missed me!”
Jane with her loot.

Another benefit of staying at the Children’s Inn is the opportunity to meet other families facing medical challenges.  The first evening we met Asia, a 5 year old girl from Italy whose twin sister had a yet-unidentified severe neuro-degenerative disorder.  Her family was at NIH looking for possible answers.  Asia did not speak any English, but that did not stop her and Jane from becoming fast friends.  She taught us how to say “Buonnanote”.  We also met Ali, another five year old who asked me in broken English what tests Jane was going to have.  He asked, “Will she have CT scan?”—making a whirring sound with his mouth and motioning his arms as if pushing an imaginary gurney into a scanner.  It occurred to me that “CT scan” should not be part of the every-day vocabulary of a five year old.

Jane and I spent nine hours at the hospital our first full day at NIH going from test to test, appointment to appointment.  Despite this she remained bouncy and smiling, reveling in the new kinds of fist-bumps she had learned from various health care workers that day.  That evening back at the Children’s Inn Jane enjoyed a magic show after dinner.
Jane with Asia (light pink), Ali (stripes) and others enjoying a show.

The following day we signed in to the hospital 8:55am and didn’t sign out of the hospital until 8:15pm.  Jane took her first dose of AZD6244 then had blood drawn at 30 mins, 1 hr, 2 hrs, 3 hrs, 5 hrs, 8 hrs, and 12 hrs after the initial dose.  Ugh.  Jane’s first grade class has learned the definition of the word stamina as being able to do something for a long time—they use it in the context of trying to extend the length of time they can read in one sitting.  I told Jane I thought she had more stamina for medical tests than any person I know.

Our final day at NIH included just a single final blood draw.  Before we headed over to the hospital Todd texted me that our insurance company sent a letter denying coverage of Gleevec after all.  This solidifies for me that we made the right decision to give AZD6244 a try.

~ ~ ~

Back at home, we set up our regimen for taking AZD6244.  We have to keep a meticulous medication diary.  Doses must be taken twice a day on an empty stomach, which is defined as one hour before eating or two hours after eating.  Doses may not be taken less than 10 hours apart.  If we miss more than 15% of the doses we will not be permitted to continue the study.

We’ve settled into the following schedule:
Mornings—I get up at 6:30am and wake Jane to take her medicine.  She swallows two tablets whole with a glass of water, then goes back to sleep.  I wake her up again at 7:30 for breakfast and to get ready for school.
Evenings—we must finish dinner by 6:30pm so that Jane has at least two hours before her 8:30 bedtime when she takes her medicine again.  As if I need any more pressure to get dinner on the table by 6pm!!

We must also document any side effects and their severity—though no one knows exactly what the side effects may be since so few people have ever taken this medicine.  Here is a list of possibilities:

The lists below show the most common and the most serious side effects that researchers know about. There might be other side effects that researchers do not yet know about. If important new side effects are found, the study doctor will discuss these with you. 
Common, some may be serious (in 100 people receiving AZD6244 hydrogen sulfate, more than 20 may have): 
Discomforts causing symptoms 
• Diarrhea 
• Nausea or the urge to vomit 
• Vomiting 
• Swelling of the arms and/or legs 
• Fatigue or tiredness 
• Acne 
• Skin rash with the presence of macules (flat discolored area) and papules (raised bump) 
Risks that may or may not cause symptoms 
• Increased blood level of an enzyme (called CPK) which may indicate muscle damage. 
Occasional, some may be serious (in 100 people receiving AZD6244 hydrogen sulfate, from 4 to 20 may have): 
Discomforts causing symptoms 
• Belly pain 
• Constipation 
• Dry mouth, skin 
• Irritation or sores somewhere in the lining of the mouth, which may cause difficulty swallowing 
• Fever 
• Bruising, bleeding 
• Loss of appetite 
• Dizziness (or sensation of lightheadedness, unsteadiness, giddiness) 
• Headache or head pain 
• Difficulty sleeping or falling asleep 
• Cough 
• Shortness of breath 
• Itching 
• High blood pressure 
• Blurred vision 
Risks that may or may not cause symptoms 
• Lack of enough red blood cells (anemia) which may cause fatigue 
• Increased blood level of a liver enzyme (ALT/SGPT)
• Increased blood level of a liver or bone enzyme (alkaline phosphatase) 
• Increased blood level of a liver enzyme (AST/SGOT) 
• Decreased number of a type of blood cell that helps to clot blood (platelet) that may result in bruising or bleeding 
• Decreased levels of a blood protein called albumin 
• Decreased blood level of magnesium 
Rare and Serious (in 100 people receiving AZD6244 hydrogen sulfate, 3 or fewer may have): 
Discomforts causing symptoms: 
• Infection, especially with dangerously low levels of a type of white blood cell (neutrophils) 
• Decrease in heart's ability to pump blood during the "active" phase of the heartbeat (systole) 
Skin toxicity may arise from exposure to the sun. To help prevent skin effects, cover any exposed body parts with light colored clothes when in the sun and use sunscreen (SPF 30) on all exposed skin. Limit exposure to the sun, especially in the middle of the day when the sun is most intense. 
There might be other side effects that we do not know about yet. These side effects could be dangerous or life threatening. We will be checking you closely to see if any side effects are happening. Side effects of drugs like AZD6244 hydrogen sulfate usually get better if the treatment is stopped, but in some cases they can be serious or long lasting. In the meantime, if you do have side effects, we may recommend medicine or treatments to try to control them and make you comfortable. 

(3/19/14  Just in case you thought we were slacking, add to Jane’s list of tests a 2-1/2 hour neuro-ophthalmology visit back at home—the third eye exam in as many weeks.  Jane hates having her eyes dilated—more than having blood work.  This doc also had no answers, but at least Jane’s eye seems to have improved on its own.)

~ ~ ~

3/25/14 Back to NIH!  Our first follow-up visit after nearly completing our first “cycle” (four weeks) of AZD6244.  This is our third trip out of state for Jane’s treatment within two months.  Thankfully it is just an overnight trip, and includes just one full day at the hospital.

The worst side effect of the medication so far is to Jane’s skin.  She’s developed several funky rashes and sensitivity to certain things that have never bothered her skin before—including the numbing medicine we use before blood draws :(  However, if that’s the worst it gets, we’ll take it.

A first this visit:  Jane WATCHED her blood being drawn instead of closing her eyes.  Actually watched the needle go into her arm without flinching.  Don’t know how that makes me feel…

Nota Bene:  If you are ever in need of chocolate milk for a reward but the Au Bon Pain at the NIH Clinical Center only has regular milk, you can ask the nice lady at the counter to give you a shot of chocolate in a separate cup in which to mix your milk :)

Running Update:
Haven’t reported on my training in a long time.  Here are the last two months—much less than it should be, but as much as I could manage.  I have a 22 mile run planned for tomorrow and then I start to taper—Boston is only three weeks away!  For those of you watching, I will be wearing bib #32024 :)

7.6 mi
(visit to Indiana 2/2-2/4)

7.6 mi
5.0 mi
10.0 mi
7.6 mi
7.5 mi
15.1 mi
7.5 mi
5.0 mi
12.0 mi
(visit to NIH 2/26-3/1)

5.0 mi
7.6 mi
7.6 mi
12.5 mi
7.2 mi
5.0 mi
18.2 mi
3.1 mi
5.0 mi
12.0 mi
(visit to NIH 3/25-3/26)

Kristy Update:
Just wanted to let you all know that I am sorry if lately I may have been distant, pre-occupied, less social than usual… One might think I should be happy—almost a month with so far manageable side effects.  In truth, I’m terrified.   And weary.