Scan shows progression, need advice.

Posted By
1/31/2014 10:45pm
View other posts by
Activity
Replies: 20
My husband, Dave, is Stage IV, dx in August 2013, and, of course, was told he has 8 months to live.  He was accepted in the Phase III, three arm double blinded Nivo+ipi, nivo, ipi, and he had the first IV on November 1st 2013.   The CT scan (Jan. 28) didn't bring us the good news we were hoping for.  Just to keep it short, some tumours decreased, some tumours increased.  No new tumours were seen.  The preliminary report shows close to 20% progression in the tumour load.  The biggest increase was noted on the liver tumour, and on the lungs nodules. Despite this, Dave feels great, energy levels are high, just like before the treatment started.  All his blood tests are normal, including the liver enzymes.  The LDH is 138 and it's been around this value since the beginning.
 
We are still part of the Trial, as Dr. strongly feels there is still a chance Dave can benefit from the trial. He is receiving an IV every two weeks, for the next six weeks, at what point he is getting scanned again.
 
My hopes are:
1. There were almost three weeks in between the base line scan and the start of the trial.  There is a very good chance the tumours grew fast in this time frame and actually, although the numbers don't reflect it, his tumours are stable in size or even a little smaller.
2. He is a slow responder to medication, and maybe the treatment will kick in soon.
 
I kept track of all the side effects he had, and he had a lot.  None of the side effects sent him to the hospital.  The only drug he took  was Reactine, 2/day, to deal with his skin rashes and itchiness. 
 
At some point I was sure he is on the combo arm (nivo plus ipi).  And then I thought he’s on nivo, and then on ipi only.  To tell you the truth...I have no idea.  I would almost prefer he was on nivo only, because that means ipi is still an option.  But if he was on the combo arm or on ipi only, well, pd1 is not available for him as a follow up.  He is BRaf positive (V600E).
 
We are very positive people, we are going to fight this with all it takes.  We are not giving up, we have an amazing life and we have all the reasons in the world to fight our fight.
I don't know how other people deal with the reality of this disease, but I am not listening to motivational tapes, or read positive and uplifting messages from the internet.  All I do in all my spare time is research, reading articles, links, blogs, fb, forums, all melanoma related.
 
 I hope from the bottom of my heart the scan in 6 weeks will show either stable or a decrease in the tumour load.  
But if there is progression, and he was on ipi, what Plan B, Plan C, and Plan D look like?
It seems the options would be:
•  Tafinlar and MEK.  That, of course if this gets approved as standard care for Braf positive patients.
-  TIL, either at NIH, Moffit, or MD Anderson
-  Vemurafenib (Zelboraf)) 
 
Now I need help from everybody involved in any of the above, or they know somebody that knows somebody:  please, let me know 
- Is there any other treatment option that in your opinion would work as well and I missed?
- what worked for you from the options listed above?
- based on what you know from your experience, or somebody else's, in what order would you do the treatments above?
 
Thank you very much for your patience and for your input.   As I said, I hope everything is going to be ok, but I need to know the answers and the options to the what ifs, it's my way of dealing, it's what keeps me going.  I have no prior experience with any kind of illness, I'm just doing what I can to take care of my man.
 
Also, english is my second language, please be kind with my grammar and choice of words.
 

Maria,

Sorry your scans haven't been what you were hoping for.  I had one of those recently as well.  Not sure how your trial is structured for the ipi/nivo arm but in my trial I had 6 nivo infusion followed by good scans, then 3 ipi infusions followed by scans which showed progression.  I'm back on the nivo now and hoping it starts working again.  Is it possible you started with ipi infusions?  If that's the case then it would not be out of the norm to have progression at the first scans.

I've been thinking about my plan A, B, C, and D a lot lately as well.  TIL is definitely one of those.  I think you should also consider IL-2 as an option.  I know it's a tough treatment and hasn't had the best reponse rates in the past but I think it's  worth considering while Dave is still strong.  Jerry has posted a couple things lately about IL-2 and vaccine combos and Il-2 and temozolomide (TMZ) combo which have shown some pretty impressive results.  I think another option is the ADC trial they are doing at Sarah Canon in Nashville (I think it is also at the Angeles Clinic and a site in Michigan). You've probably seen this but if not you can read it it here:  http://forum.melanomainternational.org/mif/viewtopic.php?f=54&t=34242

It's not hard to pick the top 3 or 4 options, the hard part is the order.  Of course you need to be careful that one choice you make isn't going to disqualify you for a more promising option.  If my trial doesn't work out I'm really thinking about a IL-2 trial.  My thinking is the Ipi and Nivo inhibitors still having some influence on my immune system may have a positive impact on the IL-2's effectiveness.  I think after that I would try TIL.

I just got a newletter from Moffitt recently and in it they mentioned getting a grant to do more TIL research so that might be a good option if you decide to go with TIL.  Dr. Weber is overseeing that program and he studied under Dr. Rosenberg at NCI for something like 12 years.

Good luck Maria.  Hopefully we can bounce ideas off one another more.  I'm not Braf positive so I'm not very knowledgeable on those options.

Brian

 

Maria,

If I was Braf positive I would really be looking hard at this trial Jerry just posted:

http://www.melanoma.org/find-support/patient-community/mpip-melanoma-patients-information-page/clinical-trial-hd-il-2

Actually, Brian, I am not a big fan of that particular clinical trial. It just doesn't make sense to me. Vemurafenib (Zelboraf) is a drug that binds to and inhibits the mutant BRAF protein inside cells. IL-2 is a hormone-type molecule that stimulates the immune system. It is not immediately apparent to me how these two totally different treatments could enhance each other. 

The same company (Prometheus) is also sponsoring a clinical trial combining ipi with IL-2 (NCT01856023). Since these are both immune-related treatments, it makes sense to me to try to combine them. Just my 2-cents.

Thanks Pat.  That's good to know.  I think the recent study released of the vaccine and IL-2 combo sound pretty promising.  I sometimes wonder/worry how much ramping up of your immune system can one's body handle.  IPI, Nivo, IL-2, and vaccine all having some effect on the body at once.  Don't know if that's too much of a good thing or not.  As Celeste often comments on being a Rattie sometimes isn't fun.  I guess it beats the alternative though.

I remember reading, probably a year or so ago, an interview with Jim Allison (the major researcher/scientist behind Yervoy) saying he thought that a combo therapy of combining a targeted drug (specifically Vemurafenib) and an immune therapy (specifically yervoy) deserved major consideration. His idea is that the targeted therapy will blast little pieces of DNA etc. off of the melanoma rapidly. Simultaneously, these bits floating around are available for the immune system to pick up and generate an immune response against, especially strengthened by Yervoy. 

IL-2 and Vemurafenib would seem to present a similar theoretical opportunity. Jerry says there are some thoughts now that NRAS is a good mutation for IL-2.

Who knows? Maybe we're also wolves baying at the moon here. As well as sharing info.

Dr. Weber from Moffitt says at this point says that combo trials in general are the way to go for melanoma, and the way he would go if he were a patient.

Hi, Kyle-

Yes, I guess that's certainly a possibility. It reminds me of the "abscopal effect" of combining radiation with immune-based therapies. The theory is that radiation kills the melanoma cells and the dead/destroyed cells release more antigens for the immune system to recognize.  

I find it simultaneously exciting and frustrating to see all these new theories and possibilities flying around. Exciting, of course, because for so long there was NOTHING new for melanoma. Frustrating because how does one decide which option to choose? Frustrating as that may be, it sure is a heck of a lot better than the choices melanoma patients had 5 years ago. 

Maria,

Two other thoughts I had on my above postings are: Does doing IL-2 negatively impact your abiliity to do TIL later since to my understanding many TIL protocols use IL-2?  I don't know the answer to that.  And secondly, in Dave's shoes I might not use a treatment with Vemurafenib right off the bat.  Because of Vemurafenibs ability to work quickly and on high tumor burdens I might keep it in my back pocket incase I got into a situation where I really needed it to bridge the gap to another treatment.

Hi, Maria-

I think that Brian has given you some very good advice. Although this first set of scans is not as good as you were hoping for, it does appear that Dave is having at least a partial response-- think about what these scans would be likely to show if Dave had had no treatment at all these last 3 months. So whatever he is getting is doing something. That's good!

It's also early days yet. Both ipi and nivo take some time to work, so it's quite possible that the next set of scans 6 weeks from now will be better. Hang in there.

That being said, you are wise to think about and plan for what comes next. Brian is right, there have been some reports that getting IL-2 after ipi or after nivo can improve the response rates. I think there is a clinical trial studying that right now. So as long as Dave is strong and healthy, following up with IL-2 might be a good option.

If you are seriously considering the TIL option, you could use the next 6 weeks to find out if Dave gets IL-2 will that disqualify him from future TIL. I heard that Moffitt just got a new grant to try TIL again so you could call both NIH and Moffitt and find out the details of their inclusion/exclusion criteria.

And lastly, the new antibody-drug conjugate (ADC) approach is promising. Not much has been published about that yet, but it is certainly worth looking in to. Personally, I would hold off on the Tafinlar + Mekinist combo for now. It has already been FDA approved so Dave can get that at any time. Since Dave does seem to be having at least a partial response to whichever checkpoint inhibitor he is getting, I would recommend trying to leverage that success before switching to a BRAF inhibitor. But then again, maybe a 1-2 punch with a completely different approach would be exactly the right thing. That is something you could discuss with your oncologist. 

Thank you very much for your kind replies.  I appreciate your desire to help us, the feeling I get reading your posts is that you are on our team and we are in this together.  It's the only bright shinning silver lining that came with the melanoma dx, the people we meet, so open hearted, so wiling to help.
 
Brian, Dave is in a BMS trial, we don't know in what arm we are, the side effects are common to both nivo and ipi.  The trial consisted in 2 cycles, 6 weeks each of them. If he is on the combo arm, then he would have received 4 doses of ipi and 6 doses of nivo, but of lower concentration than if they were administered individually. If on the nivo only, 6 doses of higher concentration, and if ipi he would have get 4 doses.
 
As I said, I can't figure out in what arm he was.  The side effects were common to both drugs.  The CT Scan was at the end of the 12 weeks of trial.  Now he is in the 3rd cycle, one IV (nivo) every 2weeks, for as long as works, or until his body can't deal with the toxicity. He will have another scan in 6 weeks.
 
A very special lady sent me some links last night about ipi and the way it works, and it was reported that patients scans showed slow growth of the tumour load up to 20 weeks, and then they tend to shrink. There is still hope the next scan will show stable or decrease of the masses. 
 
I have to look more into the IL2, the only info I got was from somebody that was enrolled in a TIL treatment and IL was used as part of the protocol.
 
I was not familiar with the ADC, I ignored everything chemo so far but that's just me being ignorant, after reading more, local chemo treatment makes a lot of sense. 
 
POW, one other thing is that maybe the reason the tumours seem bigger is the trial drugs may cause inflammation of the masses, and to my knowledge (limited, and please correct me if I'm wrong) the CT Scan can't tell apart a live tumour from one that is inflamed or necrotic. I still believe the treatment worked, at least it slowed down the beast a little, it's just that when you read so many success stories you get a little panicky when your scan is not what you hoped for.
 
Please, keep the posts coming, it's nice to have the options lying in front of you early on so you can do your research and be able to chose what's best from what is offered to you when the time comes.

Maria, interleukin-2 (IL-2) is a treatment that was FDA approved about 20 years ago. It is a hormone-type molecule that stimulates certain T-cells to proliferate. Some people swear by it because it is the only treatment that has been shown to completely cure melanoma. Most people try to avoid it because it is very toxic (too toxic for very sick people to even attempt) and the "cure" only happens to about 6% of the people who try it. The treatments have to be given in-patient in an ICU or a specialized IL-2 ward so that the side effects can be closely monitored and treated. However, since the introduction of ipi and anti-PD1, IL-2 is getting a new lease on life because it might enhance and extend the benefits of those treatments. 

Several people here have had IL-2 and at least one (Josh F) is currently on an ipi followed by IL-2 clinical trial. I"m sure you can ask them about their experiences and recommendations. Another member, Jim Breitfeller, has been a strong proponent of ipi or anti-PD1 followed by IL-2. He hasn't posted here lately, but he writes a blog called "Melanoma Missionary" that contains some very good informaton about IL-2. 

I do have one concern about IL-2 following ipi or anti-PD1. Jim Breitfeller participated in a long thread about  IL-2 here http://www.melanoma.org/find-support/patient-community/mpip-melanoma-patients-information-page/question-jim-breitfeller In it, and in his blog, he insists that IL-2 must be given 50 days after the start of ipi. It has something to do with the timing of the maturation of the "right" T-cells and Jim claims that this timing is critical for successs. I don't know any more than that about when or whether IL-2 should be given. However, it is something you might want to look into before making your treatment decisions.

Thank you, I will look into this!  This may be a realy good option, especially if Dave was on the pd1arm.  

I am not going to comment on the available options as many of the above posts address those very well... my comment is on your very first sentence. I am somewhat amazed that a doctor would say your husband has only 8 months to live now that he has reached stage IV. Maybe that were true several years ago, but I do not believe it is true today with all these new treatment options available.

I just became stage IV myself and I plan to be here for a long time. I just have too much more left to do :).

So my simple message is do not give up hope.

Kevin

Thank you Kevin, we were in shock and disbelief when we heard him!  Dave went from stage II straight to stage IV, after skin checks and Onc appointments every 6 months for two years!  I have a good understanding of statistics and probabilities to understand what the 8 months number meant, but it still hurts to hear that, and it's still the first number you see when you do a google search on the internet.

Somebody should take it upon themselves to prove all the statistics wrong, how about all of us?

Thank you Kevin, we were in shock and disbelief when we heard him!  Dave went from stage II straight to stage IV, after skin checks and Onc appointments every 6 months for two years!  I have a good understanding of statistics and probabilities to understand what the 8 months number meant, but it still hurts to hear that, and it's still the first number you see when you do a google search on the internet.

Somebody should take it upon themselves to prove all the statistics wrong, how about all of us?

Hi Maria,

So sorry that you and Dave are going through all this just now.  However, I know that he has a fabulous weapon in his anti-melanoma arsenal....and that is you.  I have one of those myself and it is without a doubt...a partner like you in melanoma mess is worth more than gold!

I am also sorry that scans demonstrated only a mixed response.  However, since your doc thinks there may be more benefit down the road, I think that it is a very hopeful thing.  I finished a nivo, NED trial at Moffitt.  Here are some things I've learned that may be helpful for you.  No matter if Dave is getting ipi or anti-PD1 or both....these agents are known for two properties that has made response rates hard to calculate using traditional standards.  They work slowly AND sometimes, even when ultimately effective, show increased size of tumors and even growth of new tumors, despite eventually eradicating the tumors completely or decreasing them significantly.  According to Dr. Weber at Moffitt, there was a guy in my study that progressed early on and was kicked off the study.  In trying to find a different course of therapy for him, Weber rescanned him...and the tumors were then shrinking....time passed and he was rescanned...tumors still shrinking.  Last I heard, he was STILL stable with no further treatment, and because his time in the trial was stopped..this continued with very few doses of medication!  (I couldn't find all my references to that case from my blog...but two are: the entry from Sunday, March 4, 2012 and Sunday Sept 9 2012.)  Additionally, Weber has often talked about needing to change the evaluation process as well as "endpoint" measurements in immunotherapy studies for these very reasons.  Many studies have noted that tumors often appear larger on scans after initiation of immunotherapies because of the accumulation of t-cells around the tumor.  So...all in all....those factors do NOT make it unreasonable to hope that Dave's tumors are actually responding to the med given and will show decreased size on subsequent scans.  With all that....I would definitely stay the course and continue your current trial at this point.

Thoughts for the future if needed:

1.  In my work and discussion with another couple on a very similar study...they talked to the doctor and found that should they fail the study, the patient would be "unblinded".  I consider this essential for making decisions about possible next treatments and feel it is most likely how your case would be handled as well, but would ask my doctor to confirm.  I would also ask about any possibility of "cross-over" should Dave need it.

2.  Weber has discussed many times (there are several reports on my blog) how many patients who do not respond to ipi....will subsequently respond to anti-PD1 and vice versa.  So, if Dave really doesn't respond to the med he is on now, He may respond to the other...later.  (I really don't understand why your husband...if he is getting only ipi now...not be allowed to take anti-PD1 later.  Apart from the difficulty of getting into a trial...since so few remain open with the single agent.  But, many patients have been taking anti-PD1 after ipi, and it seems to me that there would remain that option albeit that it may not happen until anti-PD1 is approved.)

3.  If any of Dave's lesions are superficial enough....he may want to look at (LATER...IF needed) some studies starting up with Rose Bengal...PV-10.  It is showing some pretty good results.  You inject one or so tumors with the med and they, as well as internal tumors, GO AWAY!  Pretty cool.  Too early to know too many numbers now though.  Have a recent blog post on all that.

4. I have also posted about the ADC (antibody drug conjugate) trial on my blog.  There are few openings, but a dear one of mine is in this trial and is having reduction in tumor burden, so I am very hopeful.  It is not stereotypical chemo, but rather chemo bound to a monoclonal antibody that is picked up only by the tumor cells....and like a Trojan Horse...BAM!!  Tumor cells in trouble...the rest of you...mostly...protected...from the bad drug and the bad tumor cells.

5.  Perhaps the link below will shed some light on the rationale for use of an immune therapy (IL2) along with a BRAF inhibitor (Vemurafenib).  http://clincancerres.aacrjournals.org/content/19/5/1225.abstract  The BRAF inhibitor increases the amount of melanoma antigen on the tumor cell and makes it a better target for the immune system.

6.  The MEK/BRAF combo's are now FDA approved as already mentioned.  TIL is certainly an option.  The anti-PDL1 BRAF/MEK trial is also something that seems to hold promise and may be a real possibility should you need it.

Lastly, there are many, many more trials ongoing.  I know it is a lot of work, but reviewing those options for Stage IV melanoma (as I'm sure you probably already have) might turn up something more.  Hang in there.  Yes, Brian knows me well.  Being a rattie is not easy!  It is hard and confusing, and a jump off a ledge into the unknown in even the best of cases.  Hang in there.  Talk to your docs.  Demand to know what they think.  Ask them, "What would you do next if he was your...wife, husband, etc.?"  I've used that a lot.  It gets more answers than you might get otherwise.

Wishing you my best.  Celeste

chaoticallypreciselifeloveandmelanoma.blogspot.com

Thank you Celeste, your blog was one of the first melanoma related blogs I read and it helped me a lot to understand the nature of the beast we're dealing with, and it wasn't just the medical content (thank you  for it), but it tought me how to deal with all the curved balls thrown at us, how to approach every situation with determination and grace, how to get over my naturaly reserved character and reach to people.  

Yes, we will be unblinded when the scan will show progression and the Dr. will analize the data and decide Dave is not a responder.  If Dave was on the nivo arm, then he will get ipi, which is now approved in Canada.  But if he was on the ipi arm, well, pd1 is not available here, not even on a compassionate use treatment.  I am not sure what the options are if it turns out he was on the nivo and ipi combo.

He has several superficial masses, he is actually able to feel two of them (one is half the size it was at the beginning of the treatment, he other we knew it was on the lower abdomen from the scan, but as of one week ago it started growing significantly and now he can feel it 1cm below the skin.  He also has several nodules in both lungs (increased), a mass in the liver(increased as well), a mass behind the right shoulder blade, another one in the hamstring.  We will see if he can benefit from ADC, or any other localized chemo procedure.

Of course, there are the Braf/ MEK options available as well, at any time.

i am really greatful for all the suggestions you made, lots of homework for me, but I it's all good, I hate sitting around and doing nothing.  I love our doctor, he is extremely smart and knowledgeable, and I am pretty sure he will be open to discussions re Dave's treatment. I may even be able to understand what he is saying, lol, after doing my homework!

Oh, Maria. It has to be very hard for you to watch your husband's lesions grow.  I've often thought my husband has had to suffer more than me at different points. I think the feeling of helplessness is very hard to take. I am still hoping for the best from your current treatment plan, but I am glad he has some real alternate options should he need them. Thanks for the kind words. I am glad that my blog offered some solace. Hang in there and keep us posted.

Yours, Celeste

chaoticallypreciselifeloveandmelanoma.blogspot.com

Maria, will provide more when I get back from town, but for now some general IL-2 info. 

The aim is to administer one bag every 8 hours for a maximum of 14 bags. Normally one is able to tolerate around 7 to 9 bags in the week. Normal protocol is 5 days for the first week of each of the standard three rounds, then a one or two week break. I recommend a 2 week break, before returning for the second week of each round. Scans are taken about a month after the second weeks IL-2 treatment. If less than 25% growth, they usually consider one to be responding enough to start the second round after about a two month period between week two and week one of the next round. My Oncologist takes patients into the hospital on Monday and usually discharges them on Saturday if the blood work/body functions are acceptable.

My Oncologist has worked with IL-2 since the early 1980;s and helped develop the standard protocols for when the FDA finally approved IL-2 for Melanoma in the late 1990's. You do want a Doctor and staff that are all experienced with administering IL-2. While the side effects can be rough (horrendous) if not caught as soon as they start, they can usually be controlled without one going through the extremes that could be experienced. I urge people not to try to “man it out” with the side effects. The timing for start of side effects is fairly consistent for a person. After the first few bags you should have it down and know when to expect what to happen.

As you read, I tried that once and instead of one shot, it took three and too much time to stop my bad shakes (the Rigors). I urge people to try to keep the fluids going regularly, not to have to try to catch-up after the urine flow and kidneys have started shutting down. Keeping some bananas on hand will help keep ones potassium levels up. The larger the heating pad that is available, the better. Have warm blankets available shortly after the bag is administered.

Don't be surprised if there are some hallucinations, this is not unusual. I didn't have any, but know several people that did.

If a man has a mustache I recommend shaving it before receiving the IL-2. The nasal discharge I had caused the skin of my upper lip to become raw and the mustache matted up with scabs. (First week only, knew better afterwards.) (Much rougher to cut when it is matted with scabs on raw flesh!)

If possible, someone should stay with the patient most of the time, especially for several hours after each bag of IL-2. At the first indication of either chills/coldness or nausea the nurses should be immediately notified and provide meds to counteract within a few minutes. (In less than 5 minutes)

Low blood pressure was one of most peoples main problems. On a few, the BP goes up. Learn what happens before taking any licorice. Black Licorice raises ones blood pressure (can get licorice tea) The tea is awful tasting, more palatable if mixed with another tea. The other colors of “licorice” actually contain no licorice, only the black contains actual licorice. They skip bags when the BP drops below 90.

 

Our wonderful Jane from Maine has helped many people and produced much information about IL-2 treatment at : http://melanomaresources.info/jane.html#homenotes

I do suggest being careful about the use of Atavan. On some people (me) it does not result in the desired effect. It aggravated my Mother rather than calming her. I could not function properly after taking it myself. Most people have no problem with it. It is often used in hospitals and nursing homes to “calm” older people so that they aren't “problems”.

 

My Oncologist said I could take most of my supplements during treatment but to cut out things that act as blood thinners.  They will give one many shots of blood thinners during the week of each Il-2 hospitalization. 

 

Make sure you receive Lasix (FUROSEMIDE) water pills, or another type of diuretic before you leave the hospital. This is necessary to eliminate the excess fluid that develops in ones body from the capillary leak caused by the Il-2.

Don't be surprised when after a couple of days food loses it's taste to one. The taste resumes a few days after finishing the week of IL-2.

Try to eat 2 bananas a day so your potassium levels don’t get depleted.  When mouth starts feeling sore (it's usually thrush) Magic mouthwash/lidocaine viscose

Have they said if they will be using a Bard port or a Pic line?

My story/journal is at :  http://www.carepages.com/carepages/JerryEllis

**************************************************************************************************************
I see that Janner has redone her site.  Janner, while a multiple primary person is still a stage I person, Her father is stage IV.  She is quite a Gal.  Here is her site.   She has Jane, Kim's and Stann's  info  posted along with more under her "Patient Perspectives" at:  http://www.melanomaresources.info/

Be glad to talk verbally .

I'm me, not a statistic. Praying to not be one for years yet.

Thank you Jerry, I will go over all the info you posted, including the links.  If we have to go the IL2 route I'm sure your post will be a great resource.

Thank you Jerry, I will go over all the info you posted, including the links.  If we have to go the IL2 route I'm sure your post will be a great resource.