Sunday, 6 May 2012

America, here he comes …

I mouthed off about it on here, thought about it overnight, then asked the hospital to move Adam's bone marrow biopsy and line insertion to Tuesday 15th. As it turns out it's not very likely he'll be going on this school trip to Kew anyway. He isn't due to land back at Heathrow until 6:50am on Thursday morning. I'm not sure he'll be in a fit state for a school trip a few hours later.

I've spent the whole of this past week talking to doctors here and abroad, exchanging emails, investigating clinical trials, reading literature, making plans, and working through possible scenarios. As well as being in regular contact with Adam's consultant at the Royal Marsden and going up to meet one of the research consultants there, I've also been in touch with Penn State Hershey, Children's Hospital of Philadelphia, Baylor College of Medicine, Texas Children's Hospital, and Van Andel Institute. Not entirely surprisingly I've been waking up at 4am and immediately stuff starts going round in my head. Try as I might there's little more sleep to be had once that happens.

So do we know what we're doing yet? Have we got a plan? Err, no. Well sort of. Yes and no. The immediate plan is that Alison and Adam will be flying out to Philadelphia at lunchtime on Bank Holiday Monday, on their way to Penn State Hershey Children's Hospital. One of the options we are seriously considering is a vaccine trial there. As with almost everything we're looking at now it's an early phase clinical trial. In this particular case it's a Phase I trial which means it's actual purpose is to establish tolerability and safety criteria, rather than to see whether it has any effect in treating the disease itself.

A Phase I drug trial almost always involves dose-escalation; that is the drug is given to a certain number of patients at one particular dose level and the side-effects assessed for dose-limiting toxicities (DLTs). If such toxicities are observed the maximum tolerated dose (MTD) has been found. If not, the drug is administered to a different set of patients at an increased dose. And so it continues until the MTD is found or the highest planned dose level is reached without DLTs being observed. If you're going to enrol your child on a Phase I study there is some thinking to do about the dose level at which it is currently accruing patients. Assuming the drug does have some effectiveness (which will only be known after the fact) what might the optimal dose be? The first couple of dose levels are seldom optimal, and neither is the MTD. What tends to happen is effectiveness (if there is any) is a function of dosage up to a certain level, above which higher doses have little or no marginal benefit. So one consideration in choosing whether to participate in a Phase I drug trial is to look at the dose level it is currently recruiting patients at. Keeping in mind you only get one shot, once you've participated at one dose level you can't go back and do it again at another. Which isn't to say enrolling at the first dose level is never the right thing to do. Maybe there isn't time to wait for the dose to escalate further. Maybe, as a result of pre-clinical work, or a different Phase I study, there could be good rationale for doing a lower of dose of one drug rather than a higher dose of another. It's also worth saying that even the first dose level in children is usually a good sized dose, as the drug will already have been used in adults, and the dosing in a paediatric Phase I might start at something like 80% of the normal adult dose.

Anyway, all that was a bit of an aside. The vaccine trial is a little different because all patients get the same amount of vaccine, on the same administration schedule. It's primary objective is still to assess tolerability, but there is no dose escalation. I have had other conversations about Phase I drug trials though - there are a couple running at the Royal Marsden at the moment that Adam would be eligible for. Unfortunately, though they may be the most convenient options, I don't think they're the most promising. Of course we're in unchartered waters now with no proven therapies, so there's almost nothing that's completely clear-cut. There's a new study due to open at the Marsden in the next 6 months or so that will combine an mTOR inhibitor and an IGF1R monoclonal antibody that are currently being trialled as single agents. That might be something that's of interest, but at the moment it hasn't even been determined which solid tumour types will be eligible for enrolment.

The reason for the mad dash to Penn State is that this vaccine is derived from Adam's own blood, which has to be taken before any other treatment is given that might suppress his blood counts. It takes around three to four weeks for the vaccine to be produced. We are really serious about this trial as the next option for Adam, providing (1) his bone marrow biopsies do not show heavy infiltration, and (2) his bony disease does not progress quickly over the next few weeks. So I wanted to get Adam over there as soon as possible, have his blood extracted before we did anything else treatment-wise, and get the production process started. Then when he comes back maybe we can give him a round of chemotherapy (Temozolomide/Irinotecan) in the period during which the vaccine is being made. It will take about three weeks for Adam's blood counts to recover; all these trials, vaccine or otherwise, have eligibility criteria that require platelets and neutrophils to be at a certain level. So recovery from chemo, and vaccine production, can take place at the same time. Well that's the plan at least.

I wouldn't say I've made a nuisance of myself, after all I'm just trying to do the best for my son. But I have been responsible for driving the timescales apace. The doctor in charge of the trial at Penn State has been tremendously responsive. As usual there's always some obstacle to overcome, and in this instance it was the fact that he was busy all day Wednesday, and unavoidably away on Thursday and Friday. On Friday evening we finally settled on a plan, the NB Alliance having taken care of the financial side of things earlier that day. In the end we agreed to do everything in a single day, when ordinarily it would take two. I set about scanning and sending across Adam's medical records, the US doctor set about making sure the hospital could accommodate Adam as such short notice, and our consultant at the Marsden sent across a clinical summary of Adam's care to this point.

So on Monday Alison and Adam will fly out to Philadelphia and then make their way across Pennsylvania to Hershey. They're staying at the Ronald MacDonald House (RMH) on Monday (and Tuesday) night. First thing Tuesday morning when Adam wakes up Alison will put Emla cream on his arms, to numb them in preparation for a cannula to be inserted. At 7am they have to be at the hospital. First off Adam will undergo a physical examination, then he'll have a cannula placed and have blood taken for a full blood count, and to test for a myriad of diseases including HIV and Hepatitis. If there are no problems once those results come back from the lab Alison will then get to sign the consent for the trial itself, and Adam can go down to surgery to have a vascath inserted in his groin. Once he's out of surgery and recovered from the anaesthetic they'll hook him up to an apheresis machine and extract the blood needed to produce the vaccine. Once that's done the vascath will be removed and Adam can go back to the RMH for the night. The return flight to London is scheduled to leave Philadelphia late Wednesday afternoon, getting into Heathrow just before 7am, as I mentioned earlier. Fingers crossed everything goes smoothly to plan. There's certainly no room for any delays, that's for sure! There are undoubtedly parts of this that are not going to be much fun for Adam. In fact they're going to be shit. Having a vascath put in, and removed, for starters; out of all the experiences Adam's had since this journey began that's one he'd pick out as hating more than most. And this will be the fourth time he's had it done. That said, we are trying to make it as much of an adventure as possible, rather than something to fear. A trip to America, choosing what he wants to take, what to watch on the plane. I've told him he's got to keep a diary so he can tell me all about it when he gets back.

I knew if this day came we'd have enough money to take Adam abroad. I also knew what options were out there, having researched quite extensively. The thing I was never quite sure about, however, was whether we'd have the necessary courage and decisiveness. Would we actually be able to get over the mental hurdle that there really wasn't any use sticking around and trying again in the UK? In fact, deciding to take Adam abroad has been one of the simplest decisions ever. After that it's just a question of trying to make the very best of whatever situation we find ourselves in. And at the end of the day that what life's all about, isn't it?


  1. my very best wishes to you all. i cannot possibly know how you feel. i just hope this country soon sees sense and starts offering treatment like you get in the states.

  2. My thoughts, best wishes and hopes go with Adam to the US. The courage displayed by the whole family is inspirational.

  3. Good luck with everything. Hope for the cure for all NB kids.