Postby GrouseMan » Mon Dec 09, 2013 7:00 pm
Skypup,
Unfortunately - I really don't have much information about what mutations and length a particular drug or drug combo will work for. That's mostly in the clinical arena of things, and requires large groups of people undergoing treatment for long periods and gathering up all the statistics. The FolFox/FolFir combos they have done this and based on the trials 12 cycles seemed to be about the norm for a large group of people and beyond that they don't seem to provide much further benefit from going longer statistically speaking - BUT this is statistically speaking.... Some may benefit, or by going longer not need to switch quite so soon. Others when enrolled in the trial might have already been far along in the mutation cycles, and benefited little from even the first few cycles. Remember everyone is different, but Insurance companies and oncologists that are only willing to follow the protocol will run the cycles on one, wait for progression (usually the break) and switch combo's assuming the first will no longer work because by definition you have now had progression. I think most of them take this too literally.
NOW I AM GOING TO SAY THIS LOUDLY - I AM NOT A DR of ONCOLOGY. I use to do drug discovery and my personal take is that the drugs should only be switched when the old drug combo if given in another set of cycles doesn't work at all any more. Or if you can no longer tolerate the side effects any more (ie Oxi vs Iri). I've not seen many folks on here after the 12 rounds with Oxy and maybe added Avastin go on with just 5-FU Avastin for a while without the Oxi as an example. I think that would be a lot more tolerable than switching out Oxi for Iri and maybe even Avastin for Erbitux at the same time as well, and could be of more benefit than quitting chemo for 3 to 6 months then jumping back in with something completely different. I am talking about stage IV folks not II or III on mop up chemo. Though I do see too many people progress from III to IV with liver or lung mets on this board, after having quit their chemo cycles, and moved on to monitoring. This makes me wonder if they stopped too soon, or a tiny met was already established that no one could see yet until it had a chance to grow without hindrance by some sort of chemo.
Preclinically speaking in the early days we use to see drug resistance to the cytotoxic drugs develop in a sub population of the tumor cells, that somehow always found a way to survive. Since they rapidly divide these would start to become dominate and the reason for progression. We were hitting them usually with single cytotoxins. We always wanted to know how they did it and in some instances I think we figured it out but had no way to reverse it once it occurred. Back in the early day's we didn't have the tools that we have now to figure that out. We are starting to get a better idea now, though we really know very little about everything that goes on inside a normal cell let alone a cancerous one. Now a days we are hitting them mechanistically from multiple directions, and that seems to have helped a lot. I often wonder what would happen if we mixed this up a great deal more? Would resistance occur if one week we used Oxy, the next week Iri? And also switched up Avastin, and Erbitux back and forth? Could we keep them knocked down longer with a better QOL? Could we kill them all? There are other drugs to add to the mix as well. Most not approved for colon cancer yet, but they might work well in combinations no one has tried yet either. We do try combinations often now in preclinical models with mice and If we see a benefit in a particular tumor type, that is usually the road it takes in the clinic. New drug in combination with an existing one against a particular sort of cancer, as that is most likely the fastest road to the market place. Likely it will work with other tumor types or other existing drugs, but a company can't afford to do studies with all combinations even with mice. Its way too expensive to do up front in people even by a huge pharma company. So once it's available for use in one type of cancer - some oncologists will set up a trial with another type of tumor or in combination with an existing drug. This is more cost effective as much by then is already known about each drug by itself.
What will really drive this better is if ALL patients tumors where genetically profiled, or better still more than once, after each progression to guide drug selection perhaps.
So I can be a little optimistic further out into future for others perhaps not yet diagnosed or who are Stage II or III folks, but remain pessimistic in my shorter term view concerning my wife's stage IV. I am sorry I don't have the answer you are looking for her. Its a very complex situation, and most of the time I think we are just throwing the dice, and if we are luck have weighed them in our favor sometimes. For me its better to be informed and have plenty of knowledge and understanding than not. It will let me make better decisions. Or at least try to get my wife to make better ones if I can. She isn't always receptive.
Regards,
GrouseMan
DW 53 dx Jun 2013
CT mets Liver Spleen lung. IVb CEA~110
Jul 2013 Sig Resct
8/13 FolFox,Avastin 12Tx mild sfx, Ongoing 5-FU Avastin every 3 wks.
CEA: good marker
7/7/14 CT Can't see the spleen Mets.
8/16/15 CEA Up, CT new abdominal mets. Iri, 5-FU, Avastin every 2 wks.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
1/17 CEA up again dropped from Trial, Mets growth 4-6 mm in abdomen
5/2/17 Failed second trial, Hospitalized 15 days 5/11. Home Hospice 5/26, at peace 6/4/2017
