bostonguy

While she was not on AG-120 anymore, my mother has unfortunately now entered hospice. We are glad that AG-120 provided her with at least a couple months without progression, but are sad it did not work for longer. She has not eaten in about 3 weeks and is rapidly becoming weaker and somewhat confused.

She briefly switched to dasatinib a few weeks ago, after stopping AG-120, which I was very hopeful about based on her mutations (IDH-1 and ABL translocation), however I think her disease had progressed too far by that point. I do not want to guess whether dasatinib would have worked if started earlier.

I wish the best to all of those who are personally suffering from, or who have family with, cholangiocarcinoma. I know we are on the cusp of a new era with treatment of CC. I do wish that we were a little further along so that my young mother could have benefited, but I hope at least that her suffering has contributed to the advancement of research for future generations.

Well, the PET/CT today showed multiple new small tumors in the liver. The existing tumors did not seem to have grown too much. Labs were notable only for an increased alk phos, but otherwise pretty normal.

My mom will be coming off AG-120 today. She is starting dasatinib off-label. The dasatinib trial requires two more biopsies, which she does not want to have given that she already had two for the AG-120 trial, as well as two before that (one for initial diagnosis and another for the genetics panel). Also, the trial requires a four week washout period before starting it, which doesn’t seem like a great idea for her right now.

I’ll switch my updates to the dasatinib thread (even though it is off-trial). Thanks to all for participating in the discussion in this thread. I wish everybody who remains on AG-120 good luck. There are several people at DFCI who are doing remarkably well with it and I have a lot of faith that it is a good choice for many people.

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).

Michelle, thank you for another thoughtful post.

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.

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.

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.

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.

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.

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.

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.

Has anybody here been involved with this trial? I think dasatinib will be the next thing we try for my mother if AG-120 stops working, so I am interested to hear from people who have experience being in this trial. My mother has the IDH-1 mutation, but also has an ABL1 rearrangement (not BCR/ABL, but at the same location), so this gives even more reason to believe dasatinib would be effective.

Latest results are very mixed today. My mother is feeling about the same at the moment, with stable weight.

Her alk phos is stable at 321, down from the peak of ~600, and her CEA has decreased from 11 to 5. Her WBC is also down from 14 to 8.6. Other LFTs are essentially normal. Bilirubin is stable

The one bad news is that her CA 19-9 has increased from ~1000 on 6/10 to about 17,000 as of today (7/12). The oncologists are not sure what to make of it given the dramatic improvement she had in her other labs and the fact that she clinically appears stable.

We are planning to repeat labs and do the CT scan in 2 weeks, which will be earlier than initially scheduled (was supposed to be in 4 weeks).

Given the significant improvement in her other labs, we’re keeping our fingers crossed that the CA 19-9 increase is not just due to tumor progression. She doesn’t have signs of biliary obstruction or anything else obvious to cause the increase, but CA 19-9 is not the most reliable tumor marker.

I will give an update when we get it in a couple weeks.