An unexpected joy

Good morning! Wow, what an incredible weekend. I really can't speak for anyone else but I don't think it could have been any better for me. It all started on Friday evening. After a rather late swim, both Lynley and I did not feel like cooking. It was decided that we would go out to eat. Lynley tried to convince us to eat Mexican or Italian but it was not long before our protests and chants of "cook on the table" (kiddo codename for the Tokyo Steakhouse) quickly overwhelmed her. We won, we dressed, and we left. The dinner was fun as always. Although we have seen the show 1000 times, the kids faces always light up when they make a volcano out of the onions while they are cooking. We thoroughly enjoyed our dinner and practiced some magic tricks that I had picked up earlier in the day. I thought it would be fun to teach Hayden some magic while he was in the hospital for this latest round of chemotherapy.

After dinner our raucous bunch made our way up to the hospital where we found Hayden and much of his family. The magic tricks were a hit and I think Hayden will have a great time impressing his friends, nurses, and doctors. The kids had fun while we adults sat and chatted about all that is neuroblastoma. I don't usually get to talk to families this close to diagnosis. It just never seems to work out that way and families always seem to need a little space to make the adjustment. However, it is quite a privilege to be with them as they go through those first weeks and months. Through this experience I have relived so many of my early thoughts of diagnosis. I had even forgotten some of the darker more fearful thoughts that never even made their way to my diary. Things that even I, with all of this experience, fear to write about to this day. It is a terrifying time that only another parent of a child with cancer would understand. I hope that in some way I have helped and comforted them. I pray that I am making this easier for their family.

Hayden looked great!

Saturday marked the funeral for Alexa Aigner. You might think it strange for me to say that I had such an incredible weekend when I attended such a sad event. I think so to. However, let me explain. This funeral was perhaps the saddest I have ever been to. Unfortunately, I now have experience to compare. While I take something special from every funeral I attend this one truly inspired my faith. First, Crys (mom) did an incredible job of reliving Alexa's life through words. I felt so close to her and I felt like I knew her better than I ever had before. Perhaps, Crys' incredible story telling and the realization that she was gone was why it was so unbelievably sad. Regardless, I truly felt like Alexa was at peace and I could picture her in Heaven in my mind. There was a sense of relief and joy in her memory that just made me feel like she was there. As with all of these kiddos, she touched me deeply. I know I have said it before but it was sooo sad but I left knowing that she was truly at peace. The thought of Alexa's complete unearthly joy in Heaven bathed me in comfort for the rest of the weekend.

And that was a good thing to! Lynley had plans for me and for the next 24 hours she would have me gutting and installing our new french patio doors with Dr. Bob. I don't know what it is but there is something so rewarding about milling around and banging hammers with a good friend. Bob and I had a great time ensuring that every detail of the door installation went according to plan. You may not know this but I have an old and crooked house. It is not easy fitting a square door into a rough opening which is more parallelogram than square. Regardless, by 8:00 PM we had a set of doors in place and a couple of beers in our belly. Times were good.

Sunday was much of the same. It started with laundry and dishes and then quickly progressed to more banging of hammers as we finished trimming the outside of the door. It was therapeutic. I grunted.

At 4:30 PM Chance, Truman, and Preston appeared at the door for an evening out at the Rangers game. It was just us boys. There were hot dogs, peanuts and nachos for all. For the kiddos there were also icees and cotton candy. For chance and I, another gulp of that frosty golden beverage. I grunted again.

In a nutshell, that was my weekend. A little strange. Perhaps not what was expected.

But, for me, it was purpose.

Making sense of the senseless

Good morning! Well, I am still far from being out of a severe pout concerning Alexa. Truth be told, I am still in a state of quandary. I take all of our losses particularly hard but this one, honestly, just pisses me off. I know, I know foul language in my rated 'G' diary. I just can't help it. This one is difficult to digest. I understand that children die from neuroblastoma. I have seen that more frequently than I care to go into detail. But, the point is that I understand that, sometimes, the disease wins. I also am aware that sometimes complications arise with treatment. Sometimes, side effects get the best of kids. After all, it is as toxic a therapy as you can have for any disease and more than most other cancers. The point is that I get that. I understand that sometimes the side effects from treatment win. I get that, too.

What I don't get and I can't digest is a child like Alexa. While she was not clear of disease, she was completely and utterly vibrant. Looking at her you would have had no idea of her journey, her history, or her disease. She had been through it all - high dose chemo, radiation, a nuclear reactor full of MIBG, and a slew of phase 1 trial experience. Most recently she had spent a year on ABT-751 (the next drug for me to talk about in my article.) The point being that she was on a fairly mild therapy and one with little toxicity. She had full rosy cheeks and a head full of lovely locks. In a sense she was about as healthy as you could be with refractory disease. Her immune system was in tact. She was full of life and feist.

So, what I don't get is: how is this child taken in such a short period of time and in such a way. Like I said - I understand disease related loss. I get loss from the toxicities of therapy. What I don't get is something like this. After she has been through so much, how do we lose her to an unknown bug and pneumonia. It seems like such a slap in the face. She deserved so much more.

I understand finding a cure. I understand reducing the intensity of therapy.

What do I do for Alexa?

I have purpose just not answers.

Angel Alexa

Some time my words are not enough. After reading the following post I certainly did not have anything to say. This entry is by the mother of Alexa. We know Alexa's family as we know so many that have been touched by neuroblastoma here in the Dallas / Fort Worth area. She was very loved and will always be remembered.

When I was little I dreamed about all the things I wanted to be when I grew up. I was sure I was going to be famous. I was going to sing on Broadway and light up the big screen in movies. I was going to be something the world would know and love. Now that I am grown and look back, I wish I would have known that all my dreams would come true by just being the mother of an incredible darling girl named Alexa. Alexa. My first child, my only daughter, my little pal and my heart's desire. I love you.

On Saturday when Alexa crashed for the first time, Zack and I had an extremely mournful experience. We were in shock and we were in pain and anguish for our girl. Zack went and stood by her and touched her arm. I gathered the strength to stand beside him and touch her leg and the love and peace we felt immediately calmed our fears and extinguished our pain. She was there telling us she was okay and comforting our hearts.

We knew then that she was going to go. We tried to ignore it but we knew it was coming. Yesterday when she was taking so long to recover from each suctioning we got scared. Late in the night and early this morning we both knew it was coming. Zack stared at her and stood by her side. I was overwhelmed by the urge to sleep and forget. She wasn't sick in my dreams. I slept in until 9:30 trying to ignore what was going on.

I woke up, didn't talk to anyone, kissed my girl, got dressed and stood by her bedside knowing what would come today. It was confirmed when the doctors called us into rounds and explained what they thought would be best to do for her. We agreed and went back to her room to spend time with her.

The staff closed our door and let Zack and I take a moment with her. We talked to her and told her things and read her book to her that I wrote so long ago for this very occasion. It brought a major sense of peace to both of us, especially Zack. He told me later that it was ironic that I had written that for her and for others but it turned out to help us the most. We told her to do what Jesus was telling her and that she could go and it would be okay, that we would take care of brother.

The staff crowded in and Zack and I sat on the couch ready. We did not cry. We sat there ready for our girl to tell us when it was time. She fought valiantly and tried to go, but the nurses, machines and drugs were working furiously to make her little body keep working. Finally it was time and without speaking to one another Zack and I got up at the same moment and went to her blue little body and told her to just go. The staff backed away and told us they were basically doing CPR at that time with machines. We knew she was tired. We knew it was over. What happened next was truly one of the best experiences we'll remember always.

The staff offered to let us hold her. They all worked silently and quickly to move the bed out from under her. I pulled up a rocking chair under her and they gently laid her body in my arms as Zack embraced us both. She was still shaking from the oscillator so I asked that it be clamped off. She was finally at rest. We held her for just a few moments longer and I happened to look at the clock. It was 11:20. I turned back to her, closed my eyes and laid my hand on her heart and moments later the doctor told us she was gone.

We held strong until she left and then our mourning began. Dr. Niece and other hospital staff came to love on her, family members held her. The staff was extremely gracious to us, allowing all the time we wanted. I held her and rocked her for about 5 hours before we placed her in bed for the last time.

Zack and I are at home together. We look forward to seeing our son come back home tomorrow. We will be surrounded by family and friends. As soon as we get a date and time for the service I will post it.

All we need now is prayers and time.

http://www.caringbridge.org/visit/alexaaigner

Some days purpose just doesn't seem like enough.

Horrible Kiddo Day and 4HPR/ABT-751 cont.

Before I get into another section of my article on Fenretinide and ABT-751 I have to make a formal statement.

Lynley's children acted like horrible little spoiled brats yesterday.

I am not sure what happened. I don't think there was anything in the water. They all slept well. They ate all of their meals. And, of course, we have already completely ruled out any possibility of inferior parenting. Regardless, something was foul and the kids were, um, foul-er. I was amazed at their propensity to not only be mean to each other but to be mean to their loving parents as well. This will go down in history as "Horrible Kiddo Day." From beating each other to screaming because they missed a word in junior scrabble, it was one bad behavior after another. I have never seen so many fits in a week, much less a single day. It is days like this that leave me in a quandary. I just don't know what happened to Lynley's twerps.

Okay, now that I got that off of my chest it is time to get back into my article. Yesterday, I gave a brief introduction and began the process of laying the foundation for my discussion on the Fenretinide (4HPR) / ABT-751 combination. The bulk of my discussion has centered around identifying good research. Today I will talk about the history of Fenretinide and its use in neuroblastoma. An understanding of 4HPR, what it does do, and what it doesn't is key.

WHAT DO WE REALLY KNOW ABOUT FENRETINIDE
A review of what we know about these drugs is pretty worthwhile. I often hear parents talk about 4HPR in an effort to evaluate it for their child and I rarely hear them address the issues that are, perhaps, most important to consider when evaluating this drug. By the end of this section you will know little known secrets to Fenretinide.

Fenretinide is a synthetic retinoid (vitamin A derivative.) 4HPR is believed to effect cytotoxity in cancer cells by mechanisms that include generating reactive oxygen species and by altering sphigolipid metabolism.1,2,3 4HPR has been tested in neuroblastoma patients for over 10 years. There have been several clinical studies (phase I, II, and III) in both adults and pediatrics. 4HPR has been reported to be cytotoxic to neuroblastoma, colorectal, prostate, breast, ovarian, small-cell lung cancer and both acute lymphoid and myeloid leukemias. The drug has also been tested in at least 3 different formulations. Over the years we have learned quite a bit regarding 4HPR. In neuroblastoma, we have learned that results are highly variable. We have seen some heavily pretreated relapsed children achieve significant responses and in some cases even long term remissions. Others, however, have appeared not to respond at all. A review of the literature provides some important clues to this disparity.

Interpatient Variability - It appears that drug absorption is highly variable among patients. For example, while two children may receive the same dose, the drug can actually be absorbed into the body very differently. Some children receive enough drug in their tissues to have an effect while others do not. Understanding why there is such a marked difference is the subject of several studies.

The poor bioavailability of the capsule formulation may have limited responses in clinical trials. Even high-dose schedules of the capsule formulation have obtained relatively low micromolar plasma levels with a wide interpatient variation that has complicated interpretation of response data. Thus, developing improved formulations of fenretinide that obtain higher and/or more consistent plasma levels in a more patient friendly dosing formulation could enhance 4-HPR antitumor activity. Patients that receive higher plasma levels appear to respond better.

Drug formulations - One of the problems with 4HPR is getting enough of it into pediatric patients. During early trials with the capsule formulation kids were required to take as many as 10 capsules at a time. Even at this level not all children were receiving the levels necessary to show activity. Many patients were actually showing more side effects from the corn oil in the capsules than from the drug itself. Furthermore, with so many capsules required, compliance became an issue. Many children were unable to take the amount of capsules required. In fact, one of the later studies was terminated without reaching a maximum tolerated dose due to patient noncompliance with the number of capsules that were needed to be consumed.

THE COOKIE DOUGH FORMULATION
For Fenretinide to be effective we had to find a way to get it into children with adequate absorption and at levels know to provide benefit - enter the cookie dough formulation or Lym-X-Sorb. Many think that the reason that 4HPR was tested in the new Lym-X-Sorb formulation was an effort to make the drug taste better or to simply cram more drug into our children in the hopes of achieving more effective levels. While this is partially true, the real reason for the new formulation is the Lym-X-Sorb itself. It helps the 4HPR become more bioavailable. Essentially Lym-x-sorb acts like a glove that carries the 4HPR from the stomach to the bloodstream, making the drug far more bioavailable. In mice they were able to achieve plasma levels that were 3 to 7 times higher than with the capsule formulation with the same amount of drug. It is hoped that it would provide this same effect in children. Although the phase 1 trial is ongoing at it's highest dosing levels yet, early reports indicate that the same trend is appearing in patients. The hope is that by reducing interpatient variability and increasing absorption children will be able to consistently achieve the levels of drug which have been shown in mice to defeat neuroblastoma. At adequate levels of 4HPR Lym-x-sorb in mice survival was prolonged in both chemo sensitive and highly chemo resistant cell lines.

Well, there you have it, an overview of Fenretinide. How did I do? Tomorrow I will give an overview of ABT-751 and then hopefully get into the very promising combination trial.

With hope, purpose, and lots of words.

Fenretinide and ABT-751?

I have been having a horrible time writing the latest article concerning my trip to the ANR in Japan. It is driving me absolutely batty. I have put it down and picked it up more times than I care to reflect. The irony is that in reality it really should be so easy me to author. Truth be told, I probably know more about this particular subject than I know about anything else in the world of neuroblastoma. I think the biggest problem is that it is a subject that is so often misunderstood on many different levels. I can't tell you how many people I have talked to that have completely missed the boat on the key points that you really should know about the drugs - good or bad. Parents get so wrapped up in asking the ultimate question of whether a drug works or doesn't (rightly so), that they forget to really absorb why it works when it does and why it fails when it doesn't. The answers are often missed even though they are right before our eyes. Answers are often found in the subtleties and this understanding could be the difference between a drug or therapy saving your child's life. It is for this reason that before I talk about a combination of drugs that I address the drugs individually. Let's understand why they are important. Why they work? And why they don't? When you understand this you will likely understand when this combination is important and why it could be so incredible. Mark my words, I believe more kids will live because of this combination. Period.

In the end, since I have had so much trouble writing the article I am going to commit myself to do it in my diary. Maybe here, I can get through it. Here goes!

One of the most common questions that I have received since returning from the Advances in Neuroblastoma Research Meeting in Japan is "So did you see any new promising ideas for my son or daughter?" This question mostly seems to come from parents of relapsed children but there is no doubt that the question of what is on the horizon is on the forefront of all of our minds. It might then surprise you if I told you that one of the most promising therapies to come out of the ANR centered around a drug that has been floating around from the 1960s. Most will be shocked when I tell you that I am confident that there is not as striking a set of data anywhere in xenograft mouse models of recurrent neuroblastoma. (Read that again.) You will be floored when I tell you that all of this excitement surrounds a single drug, Fenretinide (4HPR).

The one presentation generating the most excitement was entitled "Fenretinide/Lym-X-Sorb Oral Powder Combined with the Oral Microtubule Inhibitor ABT-751 is Highly Active against Multidrug-Resistant Neuroblastoma Xenografts." In the end, they found that 4HPR and ABT-751 was a well tolerated oral drug combination that was highly active against multiple recurrent neuroblastoma xenograft models. Over the years we, as parents, have seen multitudes of studies showing activity against neuroblastoma. So why is this one so special. In this article I will lay the groundwork to tell you why this discovery is so important and so promising for our kids.

WHAT IS GOOD RESEARCH?
When evaluating any type of abstract, presentation, or medical article there are some very important things to understand. First, there are many different levels of success when it comes to killing neuroblastoma cells. A study may say "kills neuroblastoma cells" but that usually means very little. It is important to note how much neuroblastoma was killed, what type of neuroblastoma cells did it kill, and finally, was the dose of drug used actually achievable in our kids. Simply put, unless the drug kills neuroblastoma a lot faster than it grows, kills in multiple resistant cell lines, and the drug can actually be given to kids in levels that have shown this killing; why would you want to put it into our kids. The US National Library of Medicine is jam packed with medical articles that show drugs killing neuroblastoma cells. However, many of the drugs kill so little of the cell population that the drug would provide little value in our kids. Many, if not most, articles also show drugs killing neuroblastoma cell lines that are so sensitive that water alone could decimate the entire colony. Often drugs are also tested in oxygen rich situations which can be great for killing neuroblastoma cells but are impossible to mimic in the human body. Many drugs are tested at levels that would never be achievable in the human body because they are so toxic they would likely induce death or toxicities so great that it would be unethical to test on any human being. There are many reasons that seemingly good titles on medical articles get us excited but there are also generally far more reasons that the actual research is less than impressive. I tell you this so that you become aware, that you become skeptical, and so you can identify meaningful research. I also use this as a bar and so that you understand that when I explain the findings of this 4HPR/ABT-751 presentation you understand how meaningful and important this research is to our kids.

I have just touched the tip of the iceberg when it comes to potential flaws in research. There are many more areas of concern but this is a good start. For an excellent overview of the ingredients of qualitative research please review the video below. Watch this video on video.google.com.


This purpose will be continued...

5 years of purpose

So, how many of you wondered why June 21st was so significant? From the emails I received, I am guessing that just about everyone knew. However, if you did not, here goes. June 21, 2003 was the date that Sydney was diagnosed with stage 4 n-myc amplified neuroblastoma. I know you can do the math but I just love saying it myself. That is exactly 5 years. Wow! To be honest, its true significance is murky. It does not offer any guarantees. It isn't a date that screams cure or means much more than the day before. However, it is a milestone and one for which we hoped and prayed. Since diagnosis it is a beacon that has sat out on the horizon and it feels so good to be here. She made it. 5 years. Incredible. I can't wait to see what the next 5, 10, and 25 will bring.

Ironically I was actually up at the hospital on Saturday. It just so happens that I was visiting with another family whose son was in transplant. That afternoon 1 or 2 of the nurses from the very first days of diagnosis were there. There we stood and chatted right outside room 3009. The very room she was diagnosed in. Had I stayed until roughly 9:00 PM I would have stood in the very shadow of our family's diagnosis. It was nice to reminisce. After all, so much of our lives were born behind those walls. To this day, I still hate that Sydney was diagnosed with neuroblastoma but I am still (surprisingly to many) so thankful for the experience. Sounds strange doesn't it? I can guarantee that there are other parents that are probably cursing those words. But, it did bring our family together. It made us stronger and, in the end, happier. We have learned to appreciate each and everyday. Personally, it has given my life meaning and purpose. It has transformed us. In this way we have been truly blessed. I am thankful for each and every gift that we have been given - from Sydney's toleration of that first round of chemotherapy to her building a carousel out of k-nex last night. We have been a lucky and blessed family.

I don't know what today holds and I certainly don't know what will lay before us tomorrow. Life offers no guarantees. Until then we will continue to live in the moment, full of purpose and appreciation. We will continue to remember that life is perspective and that we have the choice of how we live each and everyday.

Thank you for five years of purpose. May there be many, many more.

What is tomorrow anyway?

Good morning! After looking like it was going to be a day full of high drama, I am glad to report that yesterday turned out to be uneventful. I am happy to report that Claudia's mother in law made it through surgery safely in Germany. She is still being watched closely and not completely out of the woods. But, that is a great improvement over a very dire and grave situation. We were ecstatic to see her yesterday morning and obviously not only for the twerp's sake. She would take the kids for a field trip to Chuck E Cheese's to celebrate. The kids had a great time.

The next bit of drama which was averted concerned Sydney. Although some of the redness has remained on her palms, she really isn't showing any other signs of malfunction. She had a great day and afternoon and certainly seemed no worse for the wear. From her perspective it was just about the perfect day for a kiddo. You know - eggs for breakfast, trip to Chuck E Cheese's, lunch, play, swimming in the pool, dinner at McDonald's (don't ask), swim practice, cuddles and night, night. It just doesn't get much better than that.

Finally, I wouldn't be the proud papa everyone has come to expect if I did not mention that we received Sydney's Stanford Achievement Test scores in the mail yesterday afternoon. The test is one to measure her achievement. The report compares her performance to students in the same grade across the nation. This is my measuring stick. This is one of the few ways I have to really compare to see where Sydney stands. It is also a great way to identify areas that we need to work on or, God forbid, to help identify neurologic issues. Considering her history of drugs we have to keep this in the forefront of our minds and realize that it is a very real possibility. Finally, Sydney has been in treatment for 4 out of the last 5 years. She has had a lot to overcome. She has constantly taken trips across the country for therapy and had to spend mountains of time in the hospital. For her, an average below the average would be an achievement. Well, I am extremely happy to report that she did tremendously on the test. In reviewing all of the clusters she was either average or above average in every category. In fact, she did not have a single below average rating. In fact, I would even say that she was rated above average in about half of the categories. In looking at the percentile bands I am happy to announce that Sydney scored very well. In fact, she ranked in the 95th percentile in Sentence Reading, 87th in Word Reading, and 86th in total reading. It is funny. The only areas that she seemed to score lower in were areas that required listening or hearing skills. I suppose this should tell us something. Her lowest score was in Sounds and Letters where she was in the 49th percentile and Listening in the 54th percentile. I am pretty sure that this has to do with the fact that she has hearing loss but it is something we will watch. It depends so much on how the test was administered and where she was sitting. Regardless, in the end I could not be happier. It is quite and achievement for her. Heck, it is quite an achievement for kiddos that have not been through a tenth of what she has. There you go. Told you I was a proud Papa.

How many of you know what tomorrow is?

I will give you a hint. It has been five years of purpose.