One of the big pushes at the meeting was to encourage those attending to consider those clinical trials. Pharmacyclics and other pharmaceutical supporters had booths and brochures explaining the trials that they are running.
Speeches from happy patients in deep and durable remissions and from cutting edge researchers told us why clinical trials.gov should be a dog-eared bookmark on our web browser.
The poster boys for selling the risks and benefits of the trials to all patients with lymphomas were two early studies involving new CLL drugs (Ibrutinib and GS 1101) using the visually powerful waterfall plots that tell you about shrinking tumor burden.
Here is some of the early data on ibrutinib (PCI-32765) similar to what was presented. I could show similarly impressive data for GS-1101(CAL 101).
Every picture tells a story. It's easy to see at a glance that for the vast majority of the patients their tumor burden shrank dramatically.
For many of the attendees this was their first exposure to both the brave new world of tyrosine kinase inhibitors and to what could a trial do for you. I was approached by a few with questions about what was this magical medicine and how could they get in on the action.
So here is my take on clinical trials.
Now I am not talking about letting your doctor pull off a few extra tubes of blood at each visit to bank for studies down the line. Everyone should say yes to those research requests.
I am talking about therapeutic trials.
First and foremost, you must need therapy. No matter how excited you are about a new medication, the guidelines as to when to initiate or resume treatment do not change if the therapy is tried and true, cutting edge, or experimental. Maybe 30% of us will never ever need any treatment and remissions from standard chemo-immunotherapy such as FCR can be remarkably durable. If we don't need treatment, we don't need treatment.
Let's say we do need therapy and we are doing the research to find our therapy choice. Here is where my advice about picking our team of experts becomes so critical, because without a CLL guru at the helm of our ship, we may never know or have easy access to all our options. Each of the top guns in CLL aspires to be the one who discovers the next big thing, and so expect there to be some bias towards his or her own trials. This is not entirely sinister as it is what they know best, and if we are seeing that doctor already, odds are a trial at his or her facility is going to make a lot more sense than traveling across the country for a similar option with all the risks of infections, and all the expense, stress, and just inconvenience that flying and hotel rooms entails. Ask me, I am an expert with trips from Orange County to Columbus Ohio every 3 and 1/2 weeks (and there are no direct flights).
Still, there might be a better option at a distance. It is incumbent on us to do our own research on the web and at clinical trials.gov. That was certainly the circumstances in my case where my only option for ibrutinib trial was across the country. Is it fun? NO. Is it worth it? YOU BETCHA!
When we are considering a trial, understand this is not a DIY therapeutic tour, but a tightly scripted and heavily escorted guided tour. This is important. Our appointments, biopsies, and CT scans are part of a rigid schedule, and if we don't like it, well, we can always leave the trial. We shouldn't enter a trial expecting it to change to meet our particular needs. When change comes though the IRB (Institutional Review Board), it is never quick and is always very conservative. They are watching out for our safety, but are also very sensitive to not corrupt the data by changing the rules midstream.
Understand what our insurance will pay and what it will not. Often the only costs covered by the trial sponsor is the medication and special blood tests that monitor its levels. How they get away with saying that a CT scan every three months is usually and customary care for CLL and that we and/or our insurance are responsible for the costs is beyond me, but somehow they do .
Look at what doors this trial might open, and what it might close. Having had a transplant as I have shuts off a lot of options. Will the treatment in the trial preclude further treatments or trials?
If it is a multiple arm trial, we need to be comfortable with all the possible options. Are they all realistic for our circumstances or is one arm a straw man chosen because it will be easy to best and represents nothing that we would ever consider? Can we live with letting a computer program randomly decide whatever treatment we will get?
Does it offer a cross-over if we don't respond to the arm to which we are randomly assigned? I believe that less CT sans and more cross-overs would go a long way to increasing the dismal rate of enrollment in most cancer trials in the USA. Why these are persistent sore issues will be a topic for a follow-up post.
Remember we are starting with the premise that we need treatment, so we can't compare the trial option to doing nothing. We must compare it to what we would do if we weren't in the trial. And that's the rub.
Honestly, despite these caveats, for many relapsed and most refractory CLL patients and for nearly all those with 17p deletion (like me), a trial is often our very best option. It is what I chose. And I am sure glad that I did. My circumstances would likely be very different if it weren't for Clinical Trial NCT01217749 at OSU and my daily 420 mg of ibrutinib.
Another point. We should not think of trials just as a last resort when we are knocking at heaven's gate. It is sadly so rare that such a miracle save happens. Trials are much more likely to be helpful at earlier stages of the disease.
Let's be honest. If the existing therapies were so great, the pharmaceutical companies, the universities, the NIH and all the researchers would not be trying so hard to come up with new ones and there wouldn't be the 1274 CLL trials listed on clinicaltrials.gov. For comparison, strep throat is an illness we nailed decades ago with penicillin and there are only 31 trials listed, nearly all dealing with special populations such as HIV. Most of us with CLL need more research to get us better help, but for the vast majority of us with a strep throat, there are already easy cures.
What I am saying here is that is a desperate need to move the therapy ball forward, to improve our story. As Dr. Susan O'Brien succinctly said: "Those who need treatment for CLL will die of CLL." Maybe not the cold truth we wanted, but if we are ever going to change that reality, it will be through clinical trials. Conventional therapies, as good as they are, will never change that paradigm. New treatments or protocols are our only hope for a cure.
That's why small phase 1 trials, where there has been an encouraging signal from animal and cell line studies, and now we need to know about dosing and toxicities, make more sense in CLL than in CML where options are already pretty good.
Phase 2 trials are great as there is more experience with the new drug, and now the research is looking at efficacy as well as adverse events. Sometimes the new therapies are used on their own or combined with other standard medications and sometimes new dosing schedules or combos of only already approved drug are tried.
The phase 3 trials are usually the ones that compare the new therapy to standard care and often involves hundreds and hundreds of patients from multiple sites. These are the easiest to find and enroll as they are usually big, but there can be very strict inclusion and exclusion criteria.
Truth is that we help with advancing knowledge whether or not the trial brings us any direct clinical benefit. While it's a good feeling to be beneficent, it is a much better feeling to be beneficent and healthy. Choose carefully. Ask for help.
Today, in CLL, they are so many promising choices in trials. The late Dr. Hamblin implored us to think laterally and trials are one of our best way to do that.
Last point. With the increased understanding of the biology and structure of the cancerous CLL cells, the new targeted therapies that today are only available in clinical trials are often a better bet or at least an equivalent option when compared to the less specific existing chemo-immunotherapies. In other words, while we are lab rats when we enter a trial these days, odds are improving that we will be long lived lab rats.
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