Dabrafenib and Trametinib Combo, how long for side effects

My experience is similar to Eva's–minor side effects.  I also question whether it is a good idea for a Stage III patient to use these drugs–perhaps the doctor is only proposing very short term usage?  Speaking in a non-scientific/medical way, it is generally believed that you only have so much capacity for targeted therapy–questionable whether wise to use part of that capacity at Stage III.  Of course, I'm not a doctor.

Exactly my reason for questioning why she's on these meds- I think there are some trials out there using them for stage III unresectable. 

I agree with Mat and Eva. I would be very reluctant to take any BRAF inhibitor too early in the game– especially not if I was only Stage III.

When these drugs work (and they only work in about 50% of the people who take them) they work quickly but the melanoma usually becomes resistant after 6-9 months. Then what are you going to do? Even worse, in many cases, when the melanoma becomes resistant to the BRAF inhibitor it seems to become more aggressive than it was before and it starts to spread very quickly. Bad news!

It does not seem like a good idea to me to be reaching for the BRAF inhibitor whle the patient is healthy and the tumor burden is low.

I agree with Mat and Eva. I would be very reluctant to take any BRAF inhibitor too early in the game– especially not if I was only Stage III.

When these drugs work (and they only work in about 50% of the people who take them) they work quickly but the melanoma usually becomes resistant after 6-9 months. Then what are you going to do? Even worse, in many cases, when the melanoma becomes resistant to the BRAF inhibitor it seems to become more aggressive than it was before and it starts to spread very quickly. Bad news!

It does not seem like a good idea to me to be reaching for the BRAF inhibitor whle the patient is healthy and the tumor burden is low.

Correct, we're mostly just Stage IV patients or caregivers attempting to stay abreast of the latest developments and thinking.  One additional suggestion–consider consulting with one of the investigators for these drugs (e.g., Keith Flaherty at Mass General) regarding how quickly (or not) to stop the treatment, pulsating the treatment, etc.  Good luck.

Correct, we're mostly just Stage IV patients or caregivers attempting to stay abreast of the latest developments and thinking.  One additional suggestion–consider consulting with one of the investigators for these drugs (e.g., Keith Flaherty at Mass General) regarding how quickly (or not) to stop the treatment, pulsating the treatment, etc.  Good luck.

Correct, we're mostly just Stage IV patients or caregivers attempting to stay abreast of the latest developments and thinking.  One additional suggestion–consider consulting with one of the investigators for these drugs (e.g., Keith Flaherty at Mass General) regarding how quickly (or not) to stop the treatment, pulsating the treatment, etc.  Good luck.

Actually, I am a doctor. Not an oncologist or a Melanoma specialist, but still a doctor. I knew there were trials with these drugs for stage III, and it sounds like that's what you're doing? It's a little confusing- you at least looked into trials, but it sounds like you didn't actually join the trial but instead got a script from your local onc? Do I have that right? Just trying to understand your situation.

Of course all medical decisions are to be made between you, your wife, and your doctors. The posters on this forum, myself included, are simply trying to understand your case and your decision process. This second post helps quite a bit. I (and others on this forum) was/were not aware that you could get the combo for stage III without being enrolled in a trial, but it seems that you were. I also had never heard or read the theory that it can kill/remove remaining cells for stage III NED, but most of my research into the drug has been for stage IV where that is not the case.

In my first post part of my question was, how do you know if it's working if there aren't any measurable tumors? What kind of monitoring will you be doing? You've already said that doctors are "very interested in her being on the treatment". So are we, that's all anyone on here meant, or at least that's what I meant. We're all learning all the time. Sometimes something comes along we're not familiar with or someone chooses and gets an unusual course of treatment, as you have. We all just want to learn about the therapy, the decision process, and how it works out.

You're always going to get opinions and experiences from posters, but we all recognise it's your decision how to proceed. Many of us are stage IV and the recommendation is to use these drugs as a last resort and use other available treatments first because these drugs have a finite lifespan of efficacy as others have posted, so this kind of use is unfamiliar. 

Please don't take these opinions personally, including mine- I do not mean too imply that you're wrong or should be doing something else, simply trying to learn and understand.

I very much hope that these drugs do what you want them to do. I also began as a III, although it sounds like I was a more severe III than your wife. There was only interferon for options and no trials. I did interferon, and progressed to stage IV just 4 months after completing interferon. I've been fighting like there's no tomorrow since, because for me there really may not be a tomorrow. 

Best of Luck

Actually, I am a doctor. Not an oncologist or a Melanoma specialist, but still a doctor. I knew there were trials with these drugs for stage III, and it sounds like that's what you're doing? It's a little confusing- you at least looked into trials, but it sounds like you didn't actually join the trial but instead got a script from your local onc? Do I have that right? Just trying to understand your situation.

Of course all medical decisions are to be made between you, your wife, and your doctors. The posters on this forum, myself included, are simply trying to understand your case and your decision process. This second post helps quite a bit. I (and others on this forum) was/were not aware that you could get the combo for stage III without being enrolled in a trial, but it seems that you were. I also had never heard or read the theory that it can kill/remove remaining cells for stage III NED, but most of my research into the drug has been for stage IV where that is not the case.

In my first post part of my question was, how do you know if it's working if there aren't any measurable tumors? What kind of monitoring will you be doing? You've already said that doctors are "very interested in her being on the treatment". So are we, that's all anyone on here meant, or at least that's what I meant. We're all learning all the time. Sometimes something comes along we're not familiar with or someone chooses and gets an unusual course of treatment, as you have. We all just want to learn about the therapy, the decision process, and how it works out.

You're always going to get opinions and experiences from posters, but we all recognise it's your decision how to proceed. Many of us are stage IV and the recommendation is to use these drugs as a last resort and use other available treatments first because these drugs have a finite lifespan of efficacy as others have posted, so this kind of use is unfamiliar. 

Please don't take these opinions personally, including mine- I do not mean too imply that you're wrong or should be doing something else, simply trying to learn and understand.

I very much hope that these drugs do what you want them to do. I also began as a III, although it sounds like I was a more severe III than your wife. There was only interferon for options and no trials. I did interferon, and progressed to stage IV just 4 months after completing interferon. I've been fighting like there's no tomorrow since, because for me there really may not be a tomorrow. 

Best of Luck

Actually, I am a doctor. Not an oncologist or a Melanoma specialist, but still a doctor. I knew there were trials with these drugs for stage III, and it sounds like that's what you're doing? It's a little confusing- you at least looked into trials, but it sounds like you didn't actually join the trial but instead got a script from your local onc? Do I have that right? Just trying to understand your situation.

Of course all medical decisions are to be made between you, your wife, and your doctors. The posters on this forum, myself included, are simply trying to understand your case and your decision process. This second post helps quite a bit. I (and others on this forum) was/were not aware that you could get the combo for stage III without being enrolled in a trial, but it seems that you were. I also had never heard or read the theory that it can kill/remove remaining cells for stage III NED, but most of my research into the drug has been for stage IV where that is not the case.

In my first post part of my question was, how do you know if it's working if there aren't any measurable tumors? What kind of monitoring will you be doing? You've already said that doctors are "very interested in her being on the treatment". So are we, that's all anyone on here meant, or at least that's what I meant. We're all learning all the time. Sometimes something comes along we're not familiar with or someone chooses and gets an unusual course of treatment, as you have. We all just want to learn about the therapy, the decision process, and how it works out.

You're always going to get opinions and experiences from posters, but we all recognise it's your decision how to proceed. Many of us are stage IV and the recommendation is to use these drugs as a last resort and use other available treatments first because these drugs have a finite lifespan of efficacy as others have posted, so this kind of use is unfamiliar. 

Please don't take these opinions personally, including mine- I do not mean too imply that you're wrong or should be doing something else, simply trying to learn and understand.

I very much hope that these drugs do what you want them to do. I also began as a III, although it sounds like I was a more severe III than your wife. There was only interferon for options and no trials. I did interferon, and progressed to stage IV just 4 months after completing interferon. I've been fighting like there's no tomorrow since, because for me there really may not be a tomorrow. 

Best of Luck

Hi there, I too am a doctor, not an oncologist (but have treated cancers in the past), or a melanoma specialist (treated those as well), but a veterinarian.  Our medical / scientific training helps us to ask the critical questions and makes it easeier to wade through the medicalease speak.

I am stage IV NED for over 3 years.

I was also qestioning the thoughts behind using these wonder drug blockers so early in disease, but it is a very logical argument and one that is used for IL-2 which is what made me NED.

I was worried about using my "Ace in the hole" upfront and not having anything else when it didn't work.  That is the thinking that most of us are coming from.  Your doctors reasoning thus seemed different from what most of us were thinking.  I am glad because the theory makes PERFECT sense.

By eliminating the few lurker cells aka tumor burden (even if invisible), it means there are less cells with possible mutations to be resistant to the drugs, hopefully leading to a "cure" or better response / remission.

If there are only a handful of cells left to kill, perhaps there are much fewer mutations allowing mel to persist and proliferate leading to drug failure.  Mels rapid mutation rate is what gets most of us in the end, outwitting us faster than we can find the drugs to knock it back.

Thank you for this insight, I wish I had thought of it myself! *wink*.  You have your ducks in a row and a great team.  Wishing you and your wife the best.

BTW – the only reason why clinical trials mandate most participants have measurable disease is to have something to measure if there is a response or not.  Being NED is difficult for the researchers to show a drugs effectiveness or not since there is nothing to see.  It's one of the drawbacks of the scientific method, yet good for the patients.  This is a point that most patients may forget and another reason to not get treated as early as in your situation.  It is great your doc was willing to get the drugs Rx'd.  

We were considering doing the same thing, deciding on Braf or doing IL-2.  In the end I did IL-2 because if it worked, I could have a durable remission.  I did have to keep my one remaining met to follow my response to see if it worked which scared me.  If Inf is not possible for your wife, I KNOW IL-2 is a definate NO.  Hope this works out, she is a cutting edge patient :).

Hi there, I too am a doctor, not an oncologist (but have treated cancers in the past), or a melanoma specialist (treated those as well), but a veterinarian.  Our medical / scientific training helps us to ask the critical questions and makes it easeier to wade through the medicalease speak.

I am stage IV NED for over 3 years.

I was also qestioning the thoughts behind using these wonder drug blockers so early in disease, but it is a very logical argument and one that is used for IL-2 which is what made me NED.

I was worried about using my "Ace in the hole" upfront and not having anything else when it didn't work.  That is the thinking that most of us are coming from.  Your doctors reasoning thus seemed different from what most of us were thinking.  I am glad because the theory makes PERFECT sense.

By eliminating the few lurker cells aka tumor burden (even if invisible), it means there are less cells with possible mutations to be resistant to the drugs, hopefully leading to a "cure" or better response / remission.

If there are only a handful of cells left to kill, perhaps there are much fewer mutations allowing mel to persist and proliferate leading to drug failure.  Mels rapid mutation rate is what gets most of us in the end, outwitting us faster than we can find the drugs to knock it back.

Thank you for this insight, I wish I had thought of it myself! *wink*.  You have your ducks in a row and a great team.  Wishing you and your wife the best.

BTW – the only reason why clinical trials mandate most participants have measurable disease is to have something to measure if there is a response or not.  Being NED is difficult for the researchers to show a drugs effectiveness or not since there is nothing to see.  It's one of the drawbacks of the scientific method, yet good for the patients.  This is a point that most patients may forget and another reason to not get treated as early as in your situation.  It is great your doc was willing to get the drugs Rx'd.  

We were considering doing the same thing, deciding on Braf or doing IL-2.  In the end I did IL-2 because if it worked, I could have a durable remission.  I did have to keep my one remaining met to follow my response to see if it worked which scared me.  If Inf is not possible for your wife, I KNOW IL-2 is a definate NO.  Hope this works out, she is a cutting edge patient :).

Hi there, I too am a doctor, not an oncologist (but have treated cancers in the past), or a melanoma specialist (treated those as well), but a veterinarian.  Our medical / scientific training helps us to ask the critical questions and makes it easeier to wade through the medicalease speak.

I am stage IV NED for over 3 years.

I was also qestioning the thoughts behind using these wonder drug blockers so early in disease, but it is a very logical argument and one that is used for IL-2 which is what made me NED.

I was worried about using my "Ace in the hole" upfront and not having anything else when it didn't work.  That is the thinking that most of us are coming from.  Your doctors reasoning thus seemed different from what most of us were thinking.  I am glad because the theory makes PERFECT sense.

By eliminating the few lurker cells aka tumor burden (even if invisible), it means there are less cells with possible mutations to be resistant to the drugs, hopefully leading to a "cure" or better response / remission.

If there are only a handful of cells left to kill, perhaps there are much fewer mutations allowing mel to persist and proliferate leading to drug failure.  Mels rapid mutation rate is what gets most of us in the end, outwitting us faster than we can find the drugs to knock it back.

Thank you for this insight, I wish I had thought of it myself! *wink*.  You have your ducks in a row and a great team.  Wishing you and your wife the best.

BTW – the only reason why clinical trials mandate most participants have measurable disease is to have something to measure if there is a response or not.  Being NED is difficult for the researchers to show a drugs effectiveness or not since there is nothing to see.  It's one of the drawbacks of the scientific method, yet good for the patients.  This is a point that most patients may forget and another reason to not get treated as early as in your situation.  It is great your doc was willing to get the drugs Rx'd.  

We were considering doing the same thing, deciding on Braf or doing IL-2.  In the end I did IL-2 because if it worked, I could have a durable remission.  I did have to keep my one remaining met to follow my response to see if it worked which scared me.  If Inf is not possible for your wife, I KNOW IL-2 is a definate NO.  Hope this works out, she is a cutting edge patient :).

Thank you for clarifying. It is a very interesting approach and I hope it works the way everyone wants it to. How long will she be taking the medications- indefinitely, or for a finite period of time (assuming (and hoping) no new masses appear anywhere)?

Thank you for clarifying. It is a very interesting approach and I hope it works the way everyone wants it to. How long will she be taking the medications- indefinitely, or for a finite period of time (assuming (and hoping) no new masses appear anywhere)?

Thank you for clarifying. It is a very interesting approach and I hope it works the way everyone wants it to. How long will she be taking the medications- indefinitely, or for a finite period of time (assuming (and hoping) no new masses appear anywhere)?

I agree with Mat and Eva. I would be very reluctant to take any BRAF inhibitor too early in the game– especially not if I was only Stage III.

When these drugs work (and they only work in about 50% of the people who take them) they work quickly but the melanoma usually becomes resistant after 6-9 months. Then what are you going to do? Even worse, in many cases, when the melanoma becomes resistant to the BRAF inhibitor it seems to become more aggressive than it was before and it starts to spread very quickly. Bad news!

It does not seem like a good idea to me to be reaching for the BRAF inhibitor whle the patient is healthy and the tumor burden is low.

Exactly my reason for questioning why she's on these meds- I think there are some trials out there using them for stage III unresectable. 

Exactly my reason for questioning why she's on these meds- I think there are some trials out there using them for stage III unresectable. 

My experience is similar to Eva's–minor side effects.  I also question whether it is a good idea for a Stage III patient to use these drugs–perhaps the doctor is only proposing very short term usage?  Speaking in a non-scientific/medical way, it is generally believed that you only have so much capacity for targeted therapy–questionable whether wise to use part of that capacity at Stage III.  Of course, I'm not a doctor.

My experience is similar to Eva's–minor side effects.  I also question whether it is a good idea for a Stage III patient to use these drugs–perhaps the doctor is only proposing very short term usage?  Speaking in a non-scientific/medical way, it is generally believed that you only have so much capacity for targeted therapy–questionable whether wise to use part of that capacity at Stage III.  Of course, I'm not a doctor.

I was offered this trial. I am stage 3A. Micro mets to sentinal node. I turned it down.  

I was offered this trial. I am stage 3A. Micro mets to sentinal node. I turned it down.  

I was offered this trial. I am stage 3A. Micro mets to sentinal node. I turned it down.  

Initially I was offered a trial with an arm of wait or watch or a completion node dissection…I took the dissection and refused the trial because the literature stated that it may be curative for the 20% of the people who had additional mets.  Also, looking at Starz classifications and the positioning of the cancer cells within my sentinel node, they didn't go into the parachyma, and there was no extracapsulation of the tumor cells, plus there were only 1% surface area of the node had cancer cells in it.  No cells left in area of tumor, no other nodes positive.  They gave me a 75% to 80%  chance that I am cured.  The drugs are not without side effects that can be devastating.  I don't want them unless I need them.  I just got MRI/CT scans.  If they are clear as they should be, I am just going to live my life.  Lots of 3a are doing that from What I have been reading.

I have stage III and my onocolgist said teh trailed was conculed and show s it is benefical in stage III

Initially I was offered a trial with an arm of wait or watch or a completion node dissection…I took the dissection and refused the trial because the literature stated that it may be curative for the 20% of the people who had additional mets.  Also, looking at Starz classifications and the positioning of the cancer cells within my sentinel node, they didn't go into the parachyma, and there was no extracapsulation of the tumor cells, plus there were only 1% surface area of the node had cancer cells in it.  No cells left in area of tumor, no other nodes positive.  They gave me a 75% to 80%  chance that I am cured.  The drugs are not without side effects that can be devastating.  I don't want them unless I need them.  I just got MRI/CT scans.  If they are clear as they should be, I am just going to live my life.  Lots of 3a are doing that from What I have been reading.

Initially I was offered a trial with an arm of wait or watch or a completion node dissection…I took the dissection and refused the trial because the literature stated that it may be curative for the 20% of the people who had additional mets.  Also, looking at Starz classifications and the positioning of the cancer cells within my sentinel node, they didn't go into the parachyma, and there was no extracapsulation of the tumor cells, plus there were only 1% surface area of the node had cancer cells in it.  No cells left in area of tumor, no other nodes positive.  They gave me a 75% to 80%  chance that I am cured.  The drugs are not without side effects that can be devastating.  I don't want them unless I need them.  I just got MRI/CT scans.  If they are clear as they should be, I am just going to live my life.  Lots of 3a are doing that from What I have been reading.