What a week!

Let’s start with Monday: Max had his usual CBCs after school and we learned that he needed another red blood transfusion.

So we came back on Tuesday for the blood and spent the afternoon in clinic pinking-up his cheeks. That night he woke up at 3:30am and began throwing up every 20-30 minutes.

Wednesday morning we headed back to the clinic with a throw-up bin in Max’s lap and no where to leave Nic (mom and dad are not answering their phones!) who woke up with a fever that morning (no feverish kids are allowed in the Onc clinic!). We had to stop in a Jack in the Box parking lot shortly after leaving the house so Max could throw-up – yet again. I couldn’t get in touch with my Mom and Dad who usually take Nic so I phoned my sister Randee at work and gave her a job: come get Nic and find out where mom and dad are, because now I’m worried about them! (I can’t quite explain to you how truly lucky we are to have family on-call, ready and willing to help us in any way they can. Thanks, mi familia! PS – mom and dad were grocery shopping and feeling fine; they kept Nic for the rest of the day.) Max kept track and by 10:30am he had tossed his cookies (if we could only get him to eat cookies!) twelve times! He was looking very green. Poor guy. The doctor decided he had a viral bug in his tummy and there’s not much you can do except keep hydrated, which was not possible at home because he couldn’t keep anything down – not even a sip of water. He was given IV hydration for the day and sent home hoping that it was a one day bug. Nope… Max went to bed really early and slept well until about 2:00 am when he had a Code Brown (poo). No diarrhea thank goodness. Nic felt crappy all night and was up from 11:00 – 4:00am. Hannah also made a visit to our room due to a bad dream.

Mommy and Daddy were crazy tired Thursday morning when Max woke us up with a technicolor yawn. Back to the hospital again for more all-day IV hydration. I took Nic to the pediatrician while Nana sat with Max in clinic to see what his problem was: double ear infection. Ouch! Max finished up his daily hydration and we headed home late afternoon. Max continued to barf on and off through out the evening but somehow got a pretty decent nights sleep until… I dunno… 4:00am? Who’s keeping track? We can’t anymore.

So now it’s Friday and Max is still a sicky. He takes a sip of water and several sips of something in an odd color come right back up. He spent the day in clinic again getting hydrated. The question this morning was what do we do over the weekend? If we get admitted and stay the night there will be a room for sure in the ward. If not, we can’t be guaranteed that they would be able to hydrate Max. Luckily, Dr. Roberts came up with the (obvious to me now) plan of having HomeCare set us up with an IV pump and gatorade water to administer at home. Never thought I’d be happy about having an IV pump in my house…

We’re home for the weekend. Max hasn’t thrown up since this morning but has a lot of “I think I’m gonna” moments that are not fun at all. He had some interest in food today (wow!) and even ate a few chow mein noodles for dinner which was surprising. Hoping this stomach bug is working itself out of Max’s little tummy and that tomorrow brings a barf free day!



We put Max on IV Topotecan for 5 days January 28-February 1. Since then, his blood counts hit the ground and haven't gotten up to any reasonable level since. Look at his numbers in January and February and you can see the cliff dive they took right after the 5 days of Topotecan:

Legend: VMA/HVA=urine markers indicative of tumor cell activity - disregard HVA. WBC=white blood cell. RBC=red blood cell. PLT=platelets. ANC=absolute neutrophil count

His VMA level shot up to a recent high - 17.4. And just today I was admiring the nice downward trend. We'll measure again late in the week to see (hopefully) if it was a fluke. If not, it probably means that the cancer is getting active. For reference's sake, at official relapse in November '06, his VMA was only at 22 so it doesn't have much higher to go before alarm bells start to be sounded in the Mikulak household.

His VEGF, a blood factor that is an inflammatory marker signalling new blood vessel growth (angiogenesis) and thus tumor growth, has gone up from 40 on 1/14 to 113 on 2/12. The normal range is 31-86 pg/ml so something is going on. Sickness and/or an inflammatory response (ankle sprain, etc) can also raise VEGF, so its not entirely isolated to cancer activity.

Nevertheless I am personally very nervous - more so than usual. It's probably due also to the fact that we lost two precious kids the past few weeks (Eden Bruskow and Michael Haley) who were very similar to Max in that they were both taking nifurtimox for relapse and had been doing so for a while (Michael since before Max).

So, we continue to wait for Max's counts to climb so that he can get on his oral cytoxan again. In an attempt to get his counts up, we are pulling out all the stops - shark liver oil for platelets, and calf liver for RBC. The trouble is these remedies take time and he needs to get back on his chemo now.

On a more positive front, in today's WSJ an article about newer cancer drugs and some trends which these indicate medicine is heading, all of which favor the approach we are taking with the projects we are funding through MagicWater:

  • Personalized medicine - our first project in this area soon to be announced.

    "Now that we understand that everything is doggone different, I think we have to look at each patient completely," Dr. Sugarbaker says. "What we need to do is pair up the right patient with the right drug."

  • Looking at drugs developed for other, large-population (ie, adult) cancers and other diseases and testing them in neuroblastoma.

    ...progress in developing cancer drugs may require targeting them to tiny groups of patients.
There are many things in this article I disagree with also. Such as the notion that the only way to fight cancer effectively, is to do gene testing on an individual's cells to determine the appropriate treatment. But a counter-point in the article was also rendered.

"Finding a mutation in a tumor doesn't prove the mutation caused the tumor."

In the end, the only thing that matters if you are battling cancer is, "does it work?"

Study: More Complexity In Tailoring Cancer Drugs
February 26, 2008; Page B1

The genetic mutations in cancer cells may vary in every patient, a study found, suggesting that drugs will need to be tailored more finely to small groups.

The small study, by doctors at the Brigham and Women's Hospital in Boston and scientists from a gene-reading unit of Roche Holding AG, is among the first to look comprehensively at the genes in cancerous tumors to find which genes went awry. It's part of a new wave of medical studies using cheaper ways of reading DNA -- the chemical blueprint found in every cell -- that promise to change the understanding of disease.

The doctors, led by David Sugarbaker, a surgeon, examined four patients with a rare and deadly lung-sac cancer called pleural mesothelioma, which strikes about 3,000 people a year. The results were cause for hope and chagrin: of four patients studied, each patient's tumor had between two and six genes that had mutated, when compared with healthy cells from the same patient. Such mutations are thought to be causes of cancer. But every patient's tumor had a different group of mutated genes, and no gene was mutated in more than one patient.

That could explain why chemotherapy drugs work well in some patients and not at all in others, the doctors say. But it also means that progress in developing cancer drugs may require targeting them to tiny groups of patients. The study was published online yesterday by the journal Proceedings of the National Academy of Sciences.

The findings suggest that companies may find more success with drugs like Genentech Inc.'s Herceptin, which targets a genetic mutation found in about 20% of breast cancers; and Novartis AG's Gleevec, which attacks a particular mutation found in certain kinds of leukemia.

But it also raises the uncomfortable prospect that cancers in some patients may be so unusual that the cost of developing drugs to treat them might be prohibitively high based on the market that could benefit from them.

Dr. Sugarbaker argues that comprehensively surveying the mutated genes of patients' tumors might help in figuring out which existing cancer drugs can work on which patients. "Now that we understand that everything is doggone different, I think we have to look at each patient completely," Dr. Sugarbaker says. "What we need to do is pair up the right patient with the right drug."

But some geneticists say that approach isn't yet cost-effective. In the study, it cost more than
$100,000 per patient to read out a tumor's genes and compare them with healthy cells from the same person -- and that was using newer, cheaper methods of DNA reading from Roche's gene-reading division, called 454 Life Sciences. Roche is one of several companies trying to make gene-reading technology more affordable. Others, considered less reliable, offer similar technology that could, if verified, bring the cost to around $12,000 per patient, the authors of the study say.

"Whether it's at all clinically useful is way premature," says Bert Vogelstein, a cancer researcher at Johns Hopkins University who published similar research, on breast and colorectal cancers, in 2006. "The problem is interpreting the results." Finding a mutation in a tumor doesn't prove the mutation caused the tumor, Dr. Vogelstein says.

The study published yesterday said the genes examined "could be causally related to cancer." The study didn't look at every single piece of DNA in the tumor cells -- just pieces that were active.

Cancer is believed to occur when a body's DNA, or deoxyribonucleic acid, changes during the many generations of cell replication that occur as a person ages. Each of the six billion letters that make up DNA have to be copied to make a new cell.

The copying process isn't perfect, so the DNA of two different cells in the same person might have 10,000 differences, according to various estimates. Normally those copying errors are harmless, but if enough changes, or mutations, occur, a cell can turn into a cancerous tumor that takes over the body.

The National Institutes of Health is spending $100 million to fund a much larger study, called the Cancer Genome Atlas Pilot Project, that aims to map out mutated genes in brain, lung and ovarian cancers. Preliminary results may be released later this year.

Dr. Sugarbaker contends that understanding the bad genes in tumors will change the way they are classified and described. Today, physicians examine a tumor under a microscope to figure out what kind of cancer it is -- a process known as biopsy. But in the future, "that biopsy will not go under a microscope," Dr. Sugarbaker says. Instead, he says, "every patient is going to need a [DNA] sequence done on their tumor" and cancers will be classified by their mutations, rather than broad categories such as lung cancer or breast cancer.

However, Jason Bielas, a researcher at the University of Washington who has written skeptically about such studies, questions whether DNA reading is worth it. "It doesn't seem like at this point that it is cost-effective to go down any route that uses this type of data to design drugs," he says.

Yet some believe that yesterday's study and others like it suggest a future where individual physicians could order a custom drug that attacks the particular mutations in a tumor without harming healthy cells. Even today, scientists can go to the Web site of the Ambion division of Applera Corp., a gene-reading company, input the DNA code of an undesirable gene and buy a chemical that can "silence," or neuter it, in a test tube. Several companies are working on such "gene silencing" techniques -- also called RNA interference -- including Merck & Co., Alnylam Pharmaceuticals1 Inc. and Silence Therapeutics PLC. But they are far from being ready to be used on cancer patients.

"The RNA interference strategies are actually showing quite spectacular results in the laboratory," says Richard Gibbs, director of the Human Genome Sequencing Center at the Baylor College of Medicine. "This is precisely the kind of study that opens up the prospect of using these tools for intervention."

Write to Keith J. Winstein at keith.winstein@wsj.com

URL for this article:http://online.wsj.com/article/SB120399752255692957.html


Max stands up

Melissa and I attended the Rancho Santa Fe Unit Rady Children's Hospital Auxiliary annual fundraiser this past Saturday night. For cancer parents, this is our "night out" but in this case it was an enjoyable evening in its own right.

The reason why we were there wasn't because we're huge givers to RCHSD (though our insurance is!), but because Max was featured in the introductory video... you know... the one intended to break hearts and open wallets. Well, Max delivered once again. The evening's take was just north of $1.3M. It blows me away. If we could get a quarter of that for MagicWater in one night...

We'll post the video as soon as we receive a copy. It's quite good and Max of course looks very cute. The producer that put the intro video together has offered to put together a longer version that features only Max for fundraising purposes.

What would you do if this were your child?

I wanted to write an update regarding the Magic Water Project (MWP) foundation that I and a couple of other cancer parents launched in June 2007.

First some background: our mission is to discover and fund innovative treatments for neuroblastoma and medulloblastoma that are less-toxic and more effective than present standard-of-care therapies.

The reasons for doing this are clear:

  • The cure rate for neuroblastoma has not improved significantly in the last 20 year (20 years!!!! – but hey, I can blog from my cell phone so as a society we’ve got our tech priorities in order).

  • The limited number of available treatments for neuroblastoma – in particular relapsed neuroblastoma – are highly toxic to such small bodies, and a significant percentage of the kids fighting neuroblastoma with these treatments die from the side effects. To illustrate this fact, Max has received over 20x the amount by volume – not adjusted for weight - of toxic agents that Lance Armstrong received for his testicular cancer.

  • There is a significant amount of research on cancer, but not much of it gets applied to neuroblastoma and medulloblastoma. Instead, market forces favor research dollars and effort being directed at large, adult populations of cancer – breast, lung, prostate.

  • There are thus opportunities to attempt to apply a large amount of the research findings from other cancers to neuroblastoma and medulloblastoma, with the goal of quickly determining efficacy against tumor cells in the lab using cell and animal models, then making the determination if a phase 1 trial makes sense.

  • If we do all of the above, and quickly, our goal is that we will SAVE OUR KID’S LIVES!

The MWP has started hosting a quarterly meeting – a group of parents, researchers and oncologists – to discuss, decide on, and fund treatments which we think may be effective against these aggressive cancers.

Our second quarterly meeting took place January 28 in NYC. The report of this meeting, and associated presentations by the attending researchers, is available at the MagicWater Project website via the link below. If the link doesn’t work, you can select the text and copy-and-paste into your browser.


Please take a look when you have a chance, and please forward this post to anyone you think would be interested in helping us to achieve our goal. We have open volunteer positions available, and need all the support and help – financial and volunteer – that we can get. Our spring meeting will be held in San Diego April 17th, immediately after the American Association of Cancer Researchers (AACR) annual meeting at the convention center in downtown. Anyone interested in helping us in any way is welcome to attend the spring MWP meeting, just email me for details.


Jack's Essay

Get your kleenex's out. Paul Saxon's brother Jack - wise beyond his years - wrote a beautifully poignant and sad school essay on the death of his younger brother. Were I to ever express such a difficult, tender moment as good as he does... please read.


Paul Saxon Racing

Needless to say, we feel very confident about winning this year's Pinewood Derby for Pack 734. Paul Saxon, as you all know, passed away July 14, 2007. He was a huge NASCAR fan and his favorite driver was Jeff Gordon in car #24. Well, Paul, Max is doing the driving on this one, but we've got your name and number on the car to hopefully help us win the big trophy.


Your comments...

Just wanted to let you all know that we enjoy all the comments left on our posts and we wish more people would join in... don't be shy!


Eden Brunskow

What a sad week. Eden Brunskow passed away last night. She lived in Orange County too, just like Michael Haley. In fact, their dad's had offices right next door to one another. For both of their kid's to pass away so closely to one another is difficult to fathom.

Neil and I had the honor of meeting Eden and her dad Paul last October in Vermont. They were staying at the RMH in Vermont when we stopped by during the morning before our first MagicWater Project meeting there. Eden was so cute during that visit. She reminded me a lot of Max - subtle, quiet in speech and demeanor (at least at that time), but with lots to say and lots of intelligence to back up what she was saying.


"Mommy? I wonder when my cancer is going to go away?"

I don't know, honey. I just don't know.

Max's last comment to me tonight as I tucked him into bed. Funny, how he comes up with these comments at times when Andy & I are incredibly stressed about his cancer.

The topotecan we decided to add to his cocktail really hit him hard and threw us for a loop. His bone marrow seems to be way weaker than we would have ever guessed. In the two weeks since his topo treatment he's needed one red blood transfusion and two platelet transfusions and his counts continue to be low. His marrow recovery has been incredibly slow. This is one of those things we just didn't want to see happen.


Max and I got home from the hospital at about 9:30 last night. Not the idea I had for a president's weekend Sunday night but as any cancer parent will tell you - if you weren't good at being flexible before cancer, you learned real quickly once you started dealing with problems big and small.

Max got his hair buzzed on Saturday morning. The topotecan that we added to the mix is taking its toll on his body in more ways than just his bone marrow. He's off all chemo until his platelets stabilize (but not everything else - nifurtimox, celebrex, and all his other anti-inflammatories...even threw some artemisinin in for good measure). He started losing his hair again, and with it getting into his mouth at all times, he and we thought it best if we cut it mostly off. I'm not sure if he likes it, but this time, I have mixed feelings on the hair loss. Irrationally, I like to see it - visible proof that something is working (who knows if its killing cancer cells but those dang hair cells it certainly is killing!). On the other hand, I'm ready for him to be "normal" again and not stand out.

Back to the hair cut. Instead of taking Max to a kid's salon, I took him to a proper barber shop that I frequent in Solana Beach: 10 chairs lined up and staffed mostly by old guys in their 60's, 70's and I bet 80's. Nothing but sports, car, and fishing mags in the racks (Max loves the fishing mags - grouper and trout are his favs). Also, coffee and doughnuts on the weekends, and a straight-razor touch-up on the neck and around the ears. I love exposing Max to guy-stuff. He digs hanging out with the boys so much - loves the banter. Loves jokes. Loves getting and giving grief to other guys.

It's been an interesting 3-4 weeks here in San Diego - weather wise. We've been having some fabulous family outdoor adventures in January and February. Nic is a champ and able to hike quite a long distance and at a decent clip before getting tired. As he's only 2 1/2, this bodes well for the family getting out and doing some real adventuring in another 3 years or so.

This weekend, in addition to our unexpected visit to RCHSD, Max went on a couple of hikes at Torrey Pines State Reserve, and played at the beach.

Saturday outing with Cub Scouts den 6.

Sunday at 17th street, Del Mar.

Sunday night - getting platelets, tired.

Monday morning, Torrey Pines State Reserve, Red Butte (rebel base), fighting the stormtroopers.

Torrey Pines Lodge circa 1910 overlooking Carmel Valley and Torrey Pines state beach.


Sun 2/17/08 - Max coming home from Hospital!

Andy just sent me a text message that they are in the car and on their way home! Yay!

Max's platelets were low again... 16. So he stayed for a transfusion. Max had a reaction to the platelets this time wihch is why they were there so long. Toward the end of this transfusion a rash broke out on his legs so the nurses had to monitor him longer and wait for instructions from the doctor on-call. (It's quite common for kids to react to platelets. Max gets pre-medicated with bendryl and tylenol each time because he started coughing during a platelet transfusion and his throat became tight a long time ago. Now I guess we add "rash" to his reaction list.)

Blood did show up in his urine sample as well. This could've been a by-product of the low platelets so nothing is being done about it right now. We'll monitor his pee at home to make sure the blood stops with the transfusion he just received.

That's all for tonight... sleep well.

Sun 2/17/08 - Max off to hospital

Max and Andy are off to the hosptital this afternoon. Max had what appeared to be blood in his urine this morning and definitely this afternoon. The on-call doc said to bring him in for blood and urine analysis to see if his platelets are low and if he may have a urinary tract infection. Low platelets cause bleeding and easy bruising. (Platelets are in the blood to make it coagulate when you get a cut. If they're too low you just bleed.)

I'm guessing they'll be there for several hours waiting for results and even longer if he needs a platelet transfusion. We'll let ya know...


Max Medical Update

Here's what's been going on since the medical update two weeks ago:
  • Max has needed a red blood transfusion and platelet transfusion. Both dropped rapidly since the IV topo.
  • Max has had to check in at clinic every 5 days (instead of his usual 7 days) to have his blood counts monitored. His ANC has been under 500 for about week, which always sucks, because we're always on the look out for a fever which would land him in the hospital for several days.
  • Max's scalp finally let go and started letting his hair fall out - all over the pillow, all over his clothes, in his mouth and in all his hats. Andy took him to the barber shop today and had it buzzed off with a #1 guard (if you're not a guy, the #1 is the shortest you can go with the clippers before it's considered shaving).
  • Max is still feeling great, has lots of energy and is as cute as ever. He went on a beach hike with his cub scout troop this morning for 3 hours! They hiked down Torrey Pines beach and up the cliff from Flat Rock to the visitors' center then down the road and back to the car.
  • We stopped Max on Friday from taking his oral cyclo (chemo) in hopes that his blood counts will go up and he can start the oral topo and cyclo on Tuesday.


Michael Haley

We met Larry and his 6-year old son Michael in Vermont last March. Michael passed away last night at home in Orange County, CA. A wonderful blog entry on Eden Brunskow's site sums up what this all means to us.


Max Medical Update

Max started an additional chemo drug this past week to see if we can't knock that spot on his spine down. He had IV topotecan M-F and did great. We'll continue with the topotecan two weeks from now in an oral form that we can give to him from home along with the oral cytoxin he's been on since last summer. Hopefully he'll bear this combo better than the VP16 (etoposide) we tried on him a few months ago.

As for side effects, nothing yet. No overwhelming nausea... in fact his appetite increase a little(?). Isn't that strange? He ate a few things over the weekend and had mashed potatoes and 1/2 a chicken leg tonight. We're waiting to see what happens with his hair. :-( He's got a nice head o' hair right now and I'd hate to see him lose all of it again. He doesn't mind being bald anywhere except school. Too many kids stare at him and I know they don't mean to - but he looks very different bald.

He's going to the hospital tomorrow morning for a blood transfusion. He hasn't had any transfusions in quite a while. The IV topo definitely caused a drop in all his numbers.

As for Max, he looks and feels great right now. He's a regular ol' first grader to the general public. I hope everyone remembers that his outward appearance does not always reflect the battle that rages on inside his body.

It's a guessing game trying to figure out what to do to save our son. What treatments he can weather, how to tweek them to work best for Max. There is simply no plan in place for kids with recurred neuroblastoma - because the cure hasn't been found yet. This is in our minds every minute of every day.