3 ms·

I don’t know if you know the answer to this but one thing that I have noticed in any personal research into cancer therapy trials is that it seems that many org

by jcims 5y ago

I don’t know if you know the answer to this but one thing that I have noticed in any personal research into cancer therapy trials is that it seems that many organizations are looking for single drug treatments, potentially to the exclusion of including other drugs in trials. Anyone that has been through chemo knows that this is not where it ends up most of time, but it really seems like companies are trying to push monotherapies as much as possible. For example, antiangiogenic drugs that help reduce the vascularization of tumors would seem to be a perfect complement to this, but if you look at the phase 1 trial there were no other drugs included in the study. I can certainly understand why it makes sense to focus on the effects of a single pharmaceutical, but in order to blend doses they’re going to have to go back to a trial most likely to see the effects of the compound treatment. This takes time that many people don’t have.

epistasis 5y ago
Any single agent will usually need to prove itself as somewhat efficacious on its own. Almost certainly, safety (phase 1 trial) will be tried as a single agent before trying combination therapies. However, some of our best chemotherapy regimes are combinations of many agents, such as FOLFOX and FOLFIRI in colon cancer. But to get there was a long process. There is an idea of synthetic lethality, where a single gene getting shut off by a drug has no effect, but combining (the synthesis part) with a second gene getting shutoff causes cell death. This is an extreme case of epistasis (my gene name), but the challenge of doing trials with this is that the search space is quadratic or worse, rather than linear. And number of people enrolled in clinical trials is an extremely valuable resource. Which is what leads to making sure that we start with single agent trials, to prove both safety and hopefully efficacy of these single agents. The combinations come later, because they are so complex and difficult in terms of finding something with efficacy and in terms of managing side effects and adverse events.
- jcims 5y ago
  What you're saying makes complete sense. I just struggle at times with decisions like these because because there are millions of people sick today where the disease has broken through Avastin's ability to constrain tumor size and this might be what's needed to put it over the edge. On the other hand, anti-angiogenics are frequently not even made available in a post surgery context, particularly if perforations are a concern, so having some kind of agent that can throttle tumor growth without impacting compromised tissue would be a benefit. I guess there are no good answers until we can do whole body simulations to test drugs and all of their corner cases en masse.

by jcims 5y ago

epistasis 5y ago

Any single agent will usually need to prove itself as somewhat efficacious on its own. Almost certainly, safety (phase 1 trial) will be tried as a single agent before trying combination therapies. However, some of our best chemotherapy regimes are combinations of many agents, such as FOLFOX and FOLFIRI in colon cancer. But to get there was a long process. There is an idea of synthetic lethality, where a single gene getting shut off by a drug has no effect, but combining (the synthesis part) with a second gene getting shutoff causes cell death. This is an extreme case of epistasis (my gene name), but the challenge of doing trials with this is that the search space is quadratic or worse, rather than linear. And number of people enrolled in clinical trials is an extremely valuable resource. Which is what leads to making sure that we start with single agent trials, to prove both safety and hopefully efficacy of these single agents. The combinations come later, because they are so complex and difficult in terms of finding something with efficacy and in terms of managing side effects and adverse events.

jcims 5y ago
What you're saying makes complete sense. I just struggle at times with decisions like these because because there are millions of people sick today where the disease has broken through Avastin's ability to constrain tumor size and this might be what's needed to put it over the edge. On the other hand, anti-angiogenics are frequently not even made available in a post surgery context, particularly if perforations are a concern, so having some kind of agent that can throttle tumor growth without impacting compromised tissue would be a benefit. I guess there are no good answers until we can do whole body simulations to test drugs and all of their corner cases en masse.