Wednesday, October 7, 2009

Accutane - What do we really know?

Good morning! I have spent much of my morning re-researching Accutane and its use in neuroblastoma. Most-specifically I have been looking for new insights into the length of treatment. This seems to be a common question for parents. I can remember it certainly was for me and, honestly, I still wish I could get to the bottom of it. To me, Accutane represents one of the most frustrating parts of medical research. We know it works. We just don't seem to have any clue on how to use it to its best ability.

One of the great realizations for parents when they begin to near the end of therapy with their children is this relatively benign drug called Accutane. I say relative and I mean that in comparison to the high dose chemotherapy and radiation that our children have been exposed to previously. But, none the less, this drug which causes some skin issues and perceived moodiness is not nearly is caustic as most everything else they have had to that point. Sure, there are other side effects to watch out for but, again, nothing compared to what our kiddos have already seen.

Better yet, this treatment seems to come with roughly a 10% increase in survival. Seems like an easy decision. Six months of sporadic grumpiness and red peeley skin seems an easy trade at that point.

The question comes near the end of those treatments.

Why not do more?

Herein lies my frustration. Why do we only do six months? Why not less? Why not more? What is the absolute most efficacious dosing and schedule?

The fact of the matter is that we really don't know the answers to those questions. With as much science as we used to prove the Accutane increased survival we never really had the time or resources to address these questions. There are a few things we do know. We know that we need to hit a specific peak of the drug to truly be useful. This is the reason we take so much and we take it every day for two weeks. We are essentially trying to hit a certain concentration, or level within the body, that researches have seen it be effective in animal models. This is why it is so important to take full doses and to take them on time. This is also the reason that I personally (a non medical professional) advocate swallowing the pills and NOT aspirating the pills with a needle and squeezing the drug out. Without swallowing the whole pill you can not guarantee you are getting all of the drug. Furthermore, if you don't hit the drug levels, many believe we might as well not be using it at all. So, as a quick nugget of information, get the prescribed dose in.

Just getting all of the drug in is not the only issue. There is a small problem however, and that is the fact that people seem to metabolize the drug differently. Even with the same dose/weight ratio some kids achieve high concentrations and others never hit this threshold of efficacy. Could this be one of the reasons why some relapse and some do not? If we could guarantee that everyone got high enough levels could we really raise the roof on efficacy? It is a possibility and, just so you know, the COG is now collecting this information on some patients to find out.

Wow, I got off track. I meant to talk about how long our children should be taking Accutane and I ended up talking about the doses themselves. I guess this goes to show how cumbersome this topic can be. Regardless, I will write more on this topic in the days to come. Additionally, I think this would be a worthwhile topic for a seminar. I am going to write Dr. Reynold's and see if he has time in his schedule now. Maybe I could kill several birds with one stone.

There will be more to come.

My purpose is cranking now.

1 comment:

Yvonne said...

When my son finished his regular scheduled chemotherapy, 14 years ago, he was place on accutane. At that time, accutane was new and the dosage was being increased in every 12 kids to find the "safe" peak dose. My son actually experienced heart failure during this time. I can't recall now how far into the accutane schedule he was at the time of heart failure but he was at least half way. He came out of the heart failure just fine but they could never determine what was the actual cause. He had a heart biopsy to check the damage from chemo, but it was no more damage then expected after such a chemo schedule. But the one thing that stuck out to me the most, and still to this day, is the ability of accutane to cause mental retardation when these kids are in their child-bearing days as adults. I know this is a side-effect. Ironically, I have an aunt who used accutane for acne as a teenager. Her first child is autistic, her second was born with several holes in her heart and died at 6-months of age, her third is fine but her last child is severally mentally and physically retarded. I have seen this first hand. What do you hear/read about this problem that could potentially affect so many of the kids who survive when they become adults? The risk wasn't limited to the kids who use accutane but it could also potentially affect a few generations to come from that one child.
Honestly, my son has been gone 10 years now. And I follow NB research faithfully and I am frustrated that there is no more answers now or a better protocol to follow. We continue to run into that brick wall when trying to find answers. Nicholaus was treated at St Jude and also Sloan-Kettering. We saw the best results with the antibodies but I will always wish it was offered earlier in the treatment. Even at that time it was relatively new. Dr. Chung was working on his first NB vaccine, with high hopes, but to my knowledge it did not have the expected impact.