September 2, 2016 at 6:15 pm #90242mariajgbParticipant
I”m looking at trying to get my mother prescribed Keytruda off-label, as it seems that the pulmonary embolisms disqualify her from every trial I’ve looked at her going on next
For anyone who is interested, it looks like UCSF has a keytruda trial specifically for cholangiocarcinoma patients that’s enrolling now:
I do know that the pleural effusions did increase as a result of AG-120, just because her breathing improved very soon after her going off the trial. As for the pulmonary embolisms, though, you’re right, might just be a side effect of the cancer. Thanks for the info, wish the best for your mom.September 1, 2016 at 2:31 am #90241
Maria….so sorry to hear of the adverse events and thanks much for sharing the important info. Where are you going from here? Are you looking for another clinical trial?
MarionAugust 31, 2016 at 10:47 pm #90240
Maria, thanks for sharing your experiences. I wish the best for your mother. I think it seems reasonable to believe that the pleural effusions (fluid around the lung) and fatigue could be related to the drug.
However, it is also possible that the fatigue and pleural effusions were related to the cancer or the pulmonary embolisms. While there are some drugs that cause hypercoagulability (increased clotting), the greatest risk factor here is almost certainly just having cancer in the first place. All patients with cancer are at a higher risk of blood clots.
The increased size of the pulmonary arteries may have been due to the pulmonary embolisms, as these will cause increased back pressure leading to pulmonary arterial hypertension.
As a result, it seems likely that most of these findings are due to the cancer and not AG-120. I don’t say this to contradict you, but just to make sure you don’t think that doing the AG-120 somehow hurt your mother in a way you could have prevented or that it was a bad choice.
I’m sorry to hear that the drug did not work for very long in your mother. My own mother is still on the drug, but seems to be declining the past couple weeks. The first scan was good, but I am worried about the next one. We have the next scan on 9/6, at which point I anticipate we will be switching to another agent.
In our case, I think dasatinib will be next, since it has been shown to be effective in IDH-1 cholangio, and my mother also has a secondary ABL1 mutation, which happens to also be a primary target of dasatinib (though generally the ABL1 mutation is found in chronic myelogenous leukemia, not solid tumors).August 31, 2016 at 5:50 pm #90239mariajgbParticipant
My mother was enrolled in AG-120 at UT Southwestern so i thought i’d share her experience in case it’s helpful to anyone.
She was only on the drug for two months, during which time her primary side effects were increased fluid build-up around her lungs, and fatigue. Other than that she tolerated the drug fairly well. However at her 2 month scan we found that while it seemed to keep some of the tumors in her liver stable, a lymph node in her chest grew. In addition, she had two pulmonary embolisms in her lungs and evidence of mild arterial enlargement of her heart. The trial coordinators are denying that the pulmonary embolisms and the arterial enlargement were caused by the study (although she’s never had anything like that before, I supposed it could be a coincidence?). Because of the embolisms and the growth in the lymph node she was taken off the study.
Now, the biopsy that was used to test for her eligibility for the study was over two years old, so it’s possible her tumors have mutated in that time and that’s part of the reason we didn’t have great results on the study. Good luck to everyone else participating!August 25, 2016 at 4:41 pm #90238
Biliary management of CCA patients is not adequately addressed by the medical community. It will be one area of focus at our upcoming conference in Utah. Surgeons, oncologists, pathologists, nurses and advocates will work together to establish tools for quality, effectiveness and efficiency in biliary management. I hope it will then be adapted and integrated in the NCCN guidelines.
MarionAugust 25, 2016 at 11:34 am #90237deadliftParticipantbostonguy wrote:Marion, thanks for the suggestion. Fortunately my mother has minimal evidence of biliary obstruction with a total bilirubin of 0.4 (direct bili 0.1). That unfortunately means biliary decompression would be unlikely to be of much benefit. It is certainly something that is important in the management of CCA though, in particular if there are signs of cholangitis or worsening biliary obstruction.
May or may not be helpful but my wife’s nausea these days seems to be fully tied to what she eats, and when she takes her meds and supplements. She has a ton of alarms to tell her to eat, then take a pill then to eat then take a pill. She is also on narcotics so that may also make a difference, as she also has to manage the side effects of the narcotics which also cause Gi issues.
good luckAugust 18, 2016 at 3:37 am #90236
Marion, thanks for the suggestion. Fortunately my mother has minimal evidence of biliary obstruction with a total bilirubin of 0.4 (direct bili 0.1). That unfortunately means biliary decompression would be unlikely to be of much benefit. It is certainly something that is important in the management of CCA though, in particular if there are signs of cholangitis or worsening biliary obstruction.August 18, 2016 at 3:07 am #90235
bostonguy…..I would discuss with the physicians whether your mother could have biliary decompression while participating in the clinical research study.
Possible options to consider:
Percutaneous transhepatic biliary drainage
Endoscopic ultrasound-guided biliary drainage
MarionAugust 18, 2016 at 1:39 am #90234
Michelle, thank you for another thoughtful post.Mvpratt wrote:1) how is here fatigue? for me when I am tired and overwhelmed emotionally or physically it seems my nausea is off the charts? Is she able to go throughout her day or has her activities been affected by the cancer?
She retired from work a few months after the diagnosis and is essentially homebound due to the nausea. She is physically able to do all her ADLs, but her nausea gets much worse whenever she exerts herself so she ends up not wanting to move. She is fatigued most of the time, but that might also be due to the fact that the only meds she is taking currently are Ativan, and now Marinol.Mvpratt wrote:I can’t say enough that my physical state is really affected by my emotional wellbeing. Could your mother be thinking more about the severity of our diagnosis ( not well cured cancer) in relation to a new grand baby being born? The ebb and flow of emotions is really unbelievable. This could really be a new happy but stressful event for her that may be contributing to the nausea.
I absolutely think that her emotional state is contributing, but probably 50%+ of her symptoms are not linked with emotion. Sometimes she is in a decent mood but feels very unwell. When she starts to feel sad there is no question that the symptoms get worse. I think the olanzapine was undoubtedly helping even more due to the antidepressant effect, which is another reason it was too bad we had to stop it. I have tried to get her to start an antidepressant, but she is very insistent that she is not depressed, just nauseated, and it’s hard for me to push too hard.Mvpratt wrote:Is there something maybe in her history/ros that might be getting overlooked. I know that it is so tremendously hard for me to remain in the patient corner when things get more difficult for me… I try very hard not to try and lead my team. Lucky for me I have a great doc who knows me better than myself …lol. Maybe go back to how she is describing the nausea…. or keep a journal to identify if there are any common factors associated with it throughout the day. This could be really helpful.
I certainly agree. We’ve had a few different people think about the nausea, but at the end of the day nobody can come up with a great solution. She had an EGD not that long ago and it was entirely normal, so it seems likely that the nausea is entirely related just to the tumor, possibly from liver distention.Mvpratt wrote:Have you joined the FACEBOOK GROUP for patients on the AG-120 . There is a ton of first hand info on that page. I had considered applying to the trial but keeping up with the postings I have since reconsidered. Here is the site https://www.facebook.com/groups/753847751426566/
Thanks for the link. I hadn’t seen that group. There are a handful of people on AG-120 doing quite well at DFCI. There have been people on it for more than 20 months with stable disease. There are others who progressed significantly on their first scans. It seems like IDH-1 targeted therapy has huge potential, but they haven’t quite figured out who will respond and who won’t.Mvpratt wrote:The first job I had as an NP was for a neurology practice and marinol was used frequently for severe MS patients. I would think remembering those patients that the CBD oil would work better than the synthetic… Would get your mother maybe to try both and let you know … she might like getting a choice for once… lol This cancer doesn’t allow for tons of choices.
I think you’re probably right. The pure THC of Marinol doesn’t seem to be ideal. I’m planning to get her a 50/50 mix of THC/CBD oil from the dispensary. Hopefully it will work.Mvpratt wrote:Lastly congratulations on your new baby. That will certainly make your mother feel better…..
Thank you! I am extremely excited to see my mother playing with her granddaughter.googily wrote:The only thing that was working for my husband’s nausea a few weeks ago was, believe it or not, over-the-counter Benadryl.
I’m glad you were able to find something that works. I’ve written for Benadryl for patients that receive high doses of narcotics, particularly those with sickle cell disease, to prevent narcotic side-effects, but I’ve never used it for patients with cancer-related nausea. It is certainly an easy thing to try. Thanks for the suggestion.August 17, 2016 at 5:23 am #90233mvprattParticipant
I also would like to add…. I was unaware that you were a physician so please forgive repetitive information.
I also reviewed your entire thread here and had a few thoughts….bostonguy…..
1) how is here fatigue? for me when I am tired and overwhelmed emotionally or physically it seems my nausea is off the charts? Is she able to go throughout her day or has her activities been affected by the cancer?
2) I can’t say enough that my physical state is really affected by my emotional wellbeing. Could your mother be thinking more about the severity of our diagnosis ( not well cured cancer) in relation to a new grand baby being born? The ebb and flow of emotions is really unbelievable. This could really be a new happy but stressful event for her that may be contributing to the nausea.
3) Is there something maybe in her history/ros that might be getting overlooked. I know that it is so tremendously hard for me to remain in the patient corner when things get more difficult for me… I try very hard not to try and lead my team. Lucky for me I have a great doc who knows me better than myself …lol. Maybe go back to how she is describing the nausea…. or keep a journal to identify if there are any common factors associated with it throughout the day. This could be really helpful.
4) TD is so uncommon…. I know it is a worry with the reglan but you were using olanzapine which causes tons of TD and she never suffered with that side effect. GEM/CIS are great for causing terrible side effects. I am sure you have thought about an emptying study and upper endoscopy.
5) Glad to hear she is not in pain especially in her abdomen. I had to have some pain management due to the cancer returning in L5. really did a number on my leg. I have kept a low dose of narcotic at night .. I do not know her disease burden but sounds like she has been so lucky in that respect
6) WOW are those markers high but acceptable… I am fascinated at the range… there are so many folks like me that their markers never got above 150 and then there are others that have them in the thousands. Clearly though she has some inflammation somewhere… and yes I am glad for the gold standard of imaging…
7) Have you joined the FACEBOOK GROUP for patients on the AG-120 . There is a ton of first hand info on that page. I had considered applying to the trial but keeping up with the postings I have since reconsidered. Here is the site https://www.facebook.com/groups/753847751426566/
The first job I had as an NP was for a neurology practice and marinol was used frequently for severe MS patients. I would think remembering those patients that the CBD oil would work better than the synthetic… Would get your mother maybe to try both and let you know … she might like getting a choice for once… lol This cancer doesn’t allow for tons of choices.
9) I wish I had some great suggestion to help you and your mother. I am sure you will find something…… Also good luck on the rest of the trial. I am very interested to hear how it goes.
Lastly congratulations on your new baby. That will certainly make your mother feel better…..
MichelleAugust 17, 2016 at 3:02 am #90232googilyMember
The only thing that was working for my husband’s nausea a few weeks ago was, believe it or not, over-the-counter Benadryl. If you are throwing everything at the wall to see what sticks, and haven’t tried it yet, it can’t hurt. (He also received it via IV once in the ER for nausea)
Editing to add that his nausea went away when we completely reworked his meds three weeks ago (we think it was mainly the morphine and the dilaudid). He also absolutely could not handle the Zofran that dissolves under the tongue (the taste just hit him totally wrong when he was already nauseous). But just to be safe now that chemo has started, he takes the Zofran regular pill twice a day, and Ativan once before bedtime, and maybe a Benadryl at noon if he needs it.August 17, 2016 at 12:07 am #90231
Michelle, thank you for sharing your experience. As a physician, I too know that there is nothing quite like personal experience with disease. Even with all the years of training I had to go through to become a physician, I find myself a much better physician when dealing with illnesses I have direct experience with either with myself or family members.
We tried dronabinol (Marinol – synthetic THC) this evening and it seems to have worked moderately well. It didn’t quite take away the nausea, but she did have a much stronger desire to eat and said she actually enjoyed her meal. Her oncologist wants her to start taking it twice daily for now. If it doesn’t work as well as the CBD we will go back to the medical marijuana (from a dispensary) rather than the Marinol.
I agree that metoclopramide (Reglan) can be a good agent for situations such as this, however I would be worried about the side effects of QT prolongation (as you mentioned) and also tardive dyskinesia. I use it all the time with my own patients, so it’s a bit of a double standard. My mother tends to be very sensitive to side effects, and gets nervous about them, but it’s definitely on the list of drugs to try if nothing else works.
She is currently NOT taking any narcotics. She has not taken a single narcotic since this journey began. Her symptoms are primarily nausea and fatigue. She is only taking the AG-120, which is a tablet, and does not have the same issues that would lead to gastroparesis, but I think that is a very good thought and is always something people in this situation should consider.
We gave acupuncture a try, but unfortunately it wasn’t much help to her. We might give it another try if she is up for it.
Unfortunately, this nausea has been present since day one, prior to any treatment, so I don’t have any expectation for it to be perfectly treated. However, it would be great to get my mom to feel a bit better for a little while, especially with a new granddaughter due in a couple weeks that I’d like her to be able to enjoy.
Michelle, thanks again for your very thoughtful post.August 16, 2016 at 9:57 pm #90230mvprattParticipant
I have some experience with your issues so let me begin :
First let me say I am a Nurse Practitioner and a patient. This gives me a very unusual perspective at times so please forgive anything that sounds like medical advice. I will only share my experience.
So I have a ton of experience with the olanzapine. I work with inpatient psychiatric patients and that is a commonly used antipsychotic. It most definitely will cause the QT prolongation and a first degree AV block. It also causes tons of weight gain and eventually metabolic syndrome. I am sure the appetite increase was an added bonus in consideration of a cancer patient. My experience with olanzapine ( zyprexa) is that the QT prolongation really becomes an issue when there are too many other meds that are contributory also. Either way it is important to stop the olanzapine.
As far as help as other options I would recommend maybe going with Reglanl ( again the possible QT side effect) but would help with GI motility if she is on any type of narcotic and perhaps has just developed some gastropareisis( nerve damage to the GI tract). I had a similar situation as a side effect of oxcaliplatin. I am doing much better now but was really feeling awful. I also added a proton pump inhibitor such as prilosec or protonix, I too was prescribed ativan and it did work REALLY great so if it still works I suggest using it but maybe at a lesser dose with some of the other GI meds I mentioned above.
I too was give a sample of CBD oil from my brother. He live is a state where it is legal. I tried it once for sleep and was not over impressed but can see how it would help nausea. If it works then I too agree that you should use what you have. It is important for her to get proper nutrition However you can help her system accomplish that is the bottom line. I would also make sure that simple things like thrush, reflux, ulcer, and so on are not overlooked. Having cancer and going through these treatments are very stressful. This too may be contributing to the nausea. I would highly recommend that you let a clinical pharmacist review your meds to see if there is any other contributing medications that maybe could be removed and then others added in place. I find polypharmacy a big contributor in how I feel and a big issue with some of my patients. Sometimes less is more.
As far as alternative treatments go I have done both acupuncture and Reikke in the past for overall well being. I do recommend both therapies and think that this may provide some relief if your mother is open to it.
Not sure if this was helpful but I wanted to share my personal experience with nausea and what I have known to work or not work.
Good luck and keep me posted.
Michelle Pratt FNP-CAugust 16, 2016 at 12:55 pm #90229
While we are very pleased that AG-120 appears to be keeping the tumors stable, unfortunately her symptoms of primarily nausea are not improving. AG-120 does not shrink tumors much, so we don’t anticipate any improvement in the nausea.
She had been taking olanzapine, started for chemo nausea, which was actually helping a bit. Unfortunately she has some new conduction issues on her EKG, which can be due to olanzapine (and basically all antiemetics), so we had to stop it. The findings were QT prolongation and a new RBBB (right bundle branch block). She had an echo that was normal the same day (though that doesn’t always tell you anything about conduction issues, particularly a RBBB). The EKG issues resolved with cessation of olanzapine. AG-120 may cause QT prolongation according to the consent form, but I think it is more likely due to the olanzapine (or possibly the combination of both).
She gets some relief from lorazepam (Ativan), but it makes her drowsy and I think she is building a tolerance. Things that haven’t worked for the nausea: ondansetron (Zofran) and prochlorperazine (Compazine). She is resistant to trying new things.
Now we need to find something that actually helps her nausea. Against all odds I convinced her to try medical marijuana (a strain that was primarily CBD) and it provided some relief. We’re planning to continue with that if she’ll allow it.July 25, 2016 at 1:52 pm #90228
Just got the CT and PET/CT results. Amazingly, there has been interval decrease or stability in all of the lesions in the liver. There are no new lesions in the liver and there continues to be no metastatic disease anywhere throughout the torso. The PET shows decreased size of several lesions but with similar FDG avidity.
We are obviously very happy with these results. This is the first time that my mother’s CT or PET has shown stable or decreased disease. Every prior scan showed steady progression through gem/cis and FOLFOX.
I’m not sure what to make of the very elevated CA 19-9, but perhaps it is just a sign that the AG-120 is working. It’s a bigger bump than I would expect, but the CT and PET are still the gold standard.
We have not yet met with her oncologist to discuss the results at length. The appointment is tomorrow. I’ll continue to provide updates as they come up.
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