DK37 wrote:This is purely a guess but I am thinking that they may want to finish a full cycle/see CT-scans on this first dose level cohort (these first 3 patients including Belle) and then when they start the next dose cohort decide whether to potentially dose higher vs. dose more patients the same to enlarge the data set vs. potentially dose lower and/or less frequently (i.e. they in theory could decide that the first dose was already above the MTD). The protocols in clinicaltrials.gov are dynamic. They show their current plans (right now based upon pre-clinical efficacy & tox studies) but the protocols can be updated as needed based upon patient experience. Immunotherapy drugs do not automatically mean low side effects. In my eyes, their hoped for advantage is the potential for a true cure if the immune system can be successfully activated/trained to recognize a person's cancer.
Agreed - The Phase 1 trial is expressly done to attempt to find the overall best dose/schedule for effectiveness.... The data for this will be used to plan the later trials if they can find a happy medium. Keep in mind - one is playing a deadly game with the immune system, and attempting to find a balance. Immunological approached to cancer treatment has been around for a long time. Uses of the Interleukins in the 80's was once thought to be the cure everyone was looking for, but it turned out although the promise was substantial, and a hand full of spectacular results were observed this didn't pan out because it nearly killed more people than it helped. Since then we have learned a LOT more about how the immune system works, and the hope is we can make immunological effects much more specific and not result in an immunological storm if you will. The problem with cancer unlike viral, and bacteriological infections treated with vaccines, is that tumors are way too much like their normal cells they come from. Where the Immune system can easily identify the difference between normal cells and invaders, they can't so easily do so against cancer.
Another thing is that with greater tumor burden comes perhaps a greater immunological response, and side effects. There are some who believe that these immunological treatments will likely result eventually in less and less side effects as one goes through them because the tumor burden will eventually become very small and the immune system will handle it much like it does a cold or the flu eventually, finally to the point that there will be no side effects at all. Think of it this way - When you haven't had a flu shot and you get the flu, you end up with a substantial viral infection. This results in a delayed response by the immune system kicking in resulting in the symptoms you see. Fever, headaches, overall achiness, and likely GI and respiratory issues. Is it the infectious agent or the immune response that you are experiencing? Usually both, but if you have a flu shot - your immune system is already primed and the effects are much less because you don't have to rally the troops as hard because the immune system has been reacting all along to keep the infection in check and under control.
They are still trying to learn a lot about how all this will actually work. Although treatments look very good even in monkeys... Their immune system is not like ours. Every species is different so interpolating from animal studies is risky. I note that this particular treatment when studied in monkey's produced no reported side effects at what the researches considered quite a high dose.
I am hopeful that you can hang in their Belle, and end up with some very good overall benefit if at all possible.... The CEA reduction sounds like things are heading in the right direction. Any other markers being watched? That is also apparently part of the trial protocol.
Regards,
GrouseMan
