Topic: Need guidance

I know each person's case tends to be unique, but  I am - desperately - reaching out today to ask the many people who have been involved with this disease, what else can I be doing ?

In brief, we have been battling ICC for 13 months. We made very significant gains while using Gem/Cis for 8 cycles. The tumors (many dispersed plus very large tumor in left lobe) within the liver were reduced and the lymph nodes seemed to disappear. We moved to Gemcitabine alone and the tumors within the liver began to grow,

At that point we opted for a clinical trial (NCT01285037 - part D) which had shown good results in the initial phase. However, shortly after starting that trial, my wife had an allergic reaction to the chemo drug (cisplatin) which was a key part of this phase. We tried to go with the Met inhibitor drug alone (no longer paired with cisplatin). However, the tumors grew quickly in AND outside the liver. We are almost back to where we started.

We just started Folfox as the next chemo regimen. While its too early to determine its effectiveness, my understanding from all I've read is since we've been through the Gem/Cis - and can't go back, if the Folfox doesn't work, there is no other chemo regimen that I can find as the next option.

If others have gone down a similar road, what options are there beyond this chemo. We cannot do liver directed therapy at this point because the growth in the lymph nodes seems even more aggressive.

Beyond chemo, the only trial I believe would offer some potential to stem this disease is the trial (NCT01174121) that has shown promise with one of our members. I am not even sure we would qualify, but if the Folfox does not work it makes us more eligible (sadly).

I am hoping for a path that others have taken which I have not yet found.

Thanks, in advance, for your help.
Carl - for Lynn

Re: Need guidance

Dear Carl & Lynn, our dynamic duo, I am so very sorry to read this post. I wish I could suggest something new for Lynn but Teddy only had a Whipple, radiation  and Cyber Knife, never chemo. The only thing I can suggest is a new pair of eyes such as another opinion. As always I wish I had a magic wand to make everything better. Cyber hugs to you and Lynn and I hope some of our genius members have a good solid idea! {}{}{}{}{}{}{}

Teddy ~In our hearts forever~ATTITUDE is EVERYTHING
Any suggestion I offer is intended as friendly advice based solely on my own experience. Please consult your doctor for professional guidance.

Re: Need guidance

Carl,
I am sorry to be reading this. I sincerely hope FOLFOX does the trick. The main chemos I've heard of are Gemzar paired with a number of things.
Cisplatin, oxaliplatin, Xeloda, 5FU are the main drugs I've heard of, paired with each other or Gemzar. And FUDR, which is 5FU for the infusion pump.
I wish I could be of more help.

KrisJ
"Don't just have minutes in the day; have moments in time."
Any opinions I give are based on personal experiences, and are not based on medical knowledge. I strongly suggest receiving medical care and opinions.

Re: Need guidance

Carl,
I am so sorry to hear Lynn is not responding well to treatment.  I often worry about the day when Andrea’s treatment no longer works. I can’t imagine how difficult this is for you.
 
I keep a collection of thoughts and ideas for that time, and hopefully they help you.  There might be some more localized treatments you can consider, but if it needs a systemic approach, here are things I am thinking about that you might research and talk to the oncologist about:

Losartan:
Losartan is a drug that lowers blood pressure.  I mention it first because it is something you could consider right now.  It has been prescribed to millions of people, and has a good tolerance profile.
Here is an overview of the research:

http://www.cancerresearchuk.org/about-u … py-in-mice

Here is the main research article:

http://www.nature.com/ncomms/2013/13100 … s3516.html

Why am I interested in this?  During the stakeholders meeting, Christine Ferrone from MGH gave a lecture that claimed cholangiocarcinoma defends itself from the immune system by creating a barrier at the cell level.  The research paper indicates that Losartan seems to work by lowering cell collagen, increasing the ability of blood to penetrate, and ultimately allowing more chemo to be delivered.  They looked at pancreatic (which many have argued is similar to cholangio) and breast cancer cell lines in mice and noticed that the combination of losartan and chemo held the cancer in check much longer.  The results are mostly summarized in Figure 7 panel c and panel f for the pancreatic cell line.   For the pancreatic cell line, the chemotherapy they used in conjunction with Losartan was 5-FU (a component of FOLFOX).  I believe the article argues that Losartan can help chemo work again after the cancer stops reacting.  In any event, it has been shown to work in conjunction with a chemotherapy that Lynn is using, and has a reasonable tolerance profile, so based on that I think it is worth bringing up to your oncologist.

Immunotherapy

While you are waiting to see how FOLFOX does, I would definitely start looking into clinical trials.  Immunotherapy seems like a good place to look, especially if cholangio really does have an existing good immune response.  You already have identified the NIH trial (NCT01174121).  The other hot thing in immunotherapy right now seems to be PD-1 based trials.  There have been great results with other cancers for this type of drug, and reason to suspect it could work with cholangiocarcinoma given the immune response.  Merck is the furthest along with this drug, and the Merck drug got designated a “breakthrough” drug in March.  People seem to expect approval for the Merck drug (pembrolizumab aka lambrolizumab aka mk3475) later this year.  If it gets approved soon, you could try to use it off label.  If not, you could see if Lynn qualifies for a trial (e.g. NCT02054806).  Other companies are coming out with their own anti pd-1 and anti pd-L1 drugs, so I would search for other trials.  My rudimentary understanding is the tumors use PD-L1 to “turn off” nearby white blood cells and evade detection/destruction.  By suppressing PD-L1 in the body, your immune system is better able to find and kill the cancer.

Targeted therapy:

Since she was on the MET trial, I assume Lynn has gotten a genetic sequencing done on her tumor?  If not, I would definitely recommend getting it done.  There are a number of trials open based on having a particular genetic mutation (e.g. IDH, KRAS, MET, NOTCH, + lots more).  One I am focusing on is the IDH1/IDH2 mutation.  A trial was opened up in March for intrahepatic cholangiocarcinoma patients that have the IDH1 mutation:

http://www.clinicaltrials.gov/ct2/show/NCT02073994

The odds seem pretty decent for having this mutation.  If I recall correctly, the company running the trial (Agios), estimates that 20% of ICC patients carry the IDH1 mutation.  An earlier paper by Foundation Medicine indicated that IDH1/IDH2 was found in ~35% of cholangiocarcinoma patients (If you have survived a while with ICC, the odds may even be a little better of having IDH1 since this mutation seems to be associated with above average survival in other cancers).  The company had very good results with its initial trial of an IDH2 blocker and blood cancers.  The scientists seem to be pretty excited about IDH1/IDH2 blockers and cholangiocarcinoma, so that seems like one to look at.  For IDH1, my rudimentary understanding here is that cells with this mutation create IDH1 concentrations which causes immature cells to stop maturing and instead replicate (thus becoming cancerous).  By suppressing IDH1, the immature cells stop prematurely multiplying, and continue to develop into normal cells.

One thing I truly believe is that if you want a different result, you are going to have to do something different.  That is why I am a big fan of doing as many clinical trials as needed/possible to find something that works. Hopefully, some of these ideas help.

My heart goes out to you and Lynn,

Jason

PS - I think irinotecan is a common second line chemotherapy for cholangio.  Since Lynn is using FOLFOX rather than FOLFIRINOX, I assume she is not taking irinotecan?  Is there a reason for that?

Re: Need guidance

Jason,

Thanks for the information. I will look into Losartan. It will require discussion because Lynn is already on a blood pressure medication and has been for many years. We will have to discuss med conflicts, etc. But certainly worth reviewing.

Regarding Immunotherapy, as your research has probably shown, in several of these trials, a key inclusion criteria is that the systemic treatments (chemo typically) have proven ineffective. We have not crossed that point - and hopefully won't any time soon. I keep looking at these immunotherapy trials as our next path. The difficulty is knowing Lynn will have to get even worse before consideration. Ouch.

Regarding targeted therapy, we have not yet done gene sequencing - but not for a lack of trying. At the start of the clinical trial a biopsy was requested for the trial research. We asked at that time to have enough sample tissue taken so we could go through gene sequencing. However, the biopsy was pretty much botched. Which by the way caused Lynn to be in incredible pain for weeks afterward. The trial sponsor was OK going forward without it. But we decided to delay trying another biopsy mainly to let Lynn recover. It is still in our plans, but now we have to settle things down a bit before we perform another intrusive procedure. We are already dealing with pain management and new side effects.

Regarding Folfox v. Folforinox. I did not ask this question specifically but I believe the decision to go with Folfox was based on the greater toxicity of Folforinox and that Lynn already had an allergic reaction to the very toxic cisplatin. Originally, the oncologist had suggested Folforinox for Lynn prior to us starting Gem/Cis. It was then we were told of the higher toxicity level. We opted to go with the 'standard' Gem/Cis which certainly was beneficial. I also know Lynn is at a point where there is not of lot of healthy liver and while her liver functions are still good, we cannot afford the possible toxic liver reaction.

Please keep sending ideas my way. I am the type of person who wants to know the next plan even while in the midst of the current one. And right now, I don't feel comfortable that I am in that position.

Take care,
Carl

P.S. I hope your and Andrea's journey continues on a good path.

Re: Need guidance

Carl,

You mentioned the difficulty of doing genetic sequencing given the lack of biopsy sample. In researching different genetic sequencing options for my Dad, I came across a company that's doing sequencing using blood samples. The researchers came out of Stanford and are working in collaboration with several large hospitals, including UCSF. It can be worth a try. https://www.guardanthealth.com/patients.html

Best of luck to you and Lynn, I'm sending you my best wishes.

Julie

Re: Need guidance

Further to this Chemo discussion - I was diagnosed with unresectable Cholangiocarcinoma in September, 2013 and have been on a Gem/Cis regimen (Max dosae once a week for two weeks with third week off) for the past eight months; just started my 13th cycle - Liver tumors are 8 x 14 mm posteriorly in left lower lobe, 4 x 10 mm posteriorly in the right base, gastrohepatic nodes are 9 x 12 mm and low attenuation left renal lesion laterally is 14 x 21 mm - Dianosis also indicated there may also be a couple of lung mets floating around but that's not definite -
Just had my third CT scan followup a couple of weeks ago and it confirmed there have been basically no changes in tumor sizes and no new tumors since my diagnosis - Chemo has gone easily for me with basically no side effects except fatigue every now and then - I'm 81 years old and in basically good health - Inasmuch as my quality of life continues to be good I plan make no treatment changes always hoping my tumors remain stable - However, my ONC has suggested I consider a second opinion from Mayo or some such more experienced Cholangio group who might suggest a more aggressive treatment program although I suspect he feels we're doing just fine under the circumstances and is only making that suggestion because he feels it is his duty -
I''ve always been absolutely amazed by the knowledge and experience of those who post here and I'd appreciate any thoughts, comments or suggestions you'd care to care to make inasmuch as I'm having difficulty deciding how to proceed -

Re: Need guidance

I've been taking Losartan Potassium for a number of years for blood pressure control.  Recently, the amount I was taking (100 mg) was downsized to 25 mg and my BP has been absolutely the same as before.  Now, I'm wondering if it would be better to be on the larger dosage again.  I feel good on the drug.....can't say that I have any side effects I've noticed and the class of drugs also tends to protect the kidneys.  (Note that I am also a diabetic, so the kidney protection was a good side effect and I'm hoping it also protects my kidneys some from the chemo, though I don't know if that is the case).  I also take Atenolol to control irregular heart beats and have had no problems combining drugs for heart therapy.  Many times doctors add another heart drug for BP rather than up the dosage of the one or two already used.

"Just for today, I can get through anything."  Hey....I'm a cancer survivor, not a doctor.  The opinions I state are my own, based on my personal experiences or knowledge.  As always, talk to your doctor about your concerns and treatment.

Re: Need guidance

Julie,

Thanks for that info. I will look into this as an alternative to another biopsy.

Carl

Re: Need guidance

Carl,

In lieu of a biopsy, you could look for the IDH mutation via a blood test.  I have seen a number of papers linking the IDH1/2 mutation to 2-hydroxyglutarate (2HG) levels in the blood.  Here is one for example:

http://www.ncbi.nlm.nih.gov/pubmed/23641016

I do not know how difficult it is to get a blood test that looks for 2HG, but it might be something to track down if a sequencing is not possible.  The level of 2HG does seem to correlate with tumor burden, so that would be a consideration as well.

Jason

Re: Need guidance

Has anyone on the boards used the blood sample version of the DNA testing?  I came upon that during some reading on line and wondered about it, but couldn't find a lot of information.  I think I would do it in a heartbeat if costs were within reason and it is legitimate. 

As for the Losartan....if I understand it correctly, the idea is that it could make the chemo more effective.  We can only hope.  I'm going to be discussing it more with my oncologist. 

Julie

"Just for today, I can get through anything."  Hey....I'm a cancer survivor, not a doctor.  The opinions I state are my own, based on my personal experiences or knowledge.  As always, talk to your doctor about your concerns and treatment.

Re: Need guidance

Jason,

Thanks my friend. We provided the info regarding Losartan and its benefits with chemo to Lynn's doctor. He immediately switched her from Lisinopril to Losartan.

It is yet another small step on the road to recovery. That is our new goal. Let's take a small step each day that moves us closer to recovery.

Carl

Re: Need guidance

Yes, Carl, everything is in small steps but I hope they turn in to giant leaps for Lynn. Thinking about the 2 of you often!

Teddy ~In our hearts forever~ATTITUDE is EVERYTHING
Any suggestion I offer is intended as friendly advice based solely on my own experience. Please consult your doctor for professional guidance.

Re: Need guidance

II'd eally appreciate it if someone could give me some input in response to my earlier post (No 7 on this string) in connection with my chemotherapy treatment - Thanks very much -

Re: Need guidance

Adjuster11,

If you are stable or better, and handling the chemo really well, then I would be surprised if any changes are recommended.

Having said that, I still think it is important to have your case reviewed by a multi-disciplinary team at a major cancer center.  Even though they may not recommend changes, you never know what they will come up with.

Another advantage of visiting a major cancer center now is that you will have made future second opinions much easier (they will already have most of your records, you will have a patient ID, you will know an oncologist there, etc.)  If something changes with your condition, it will be much easier to get Mayo's quick take on the situation if you have already made contact with them.

Keep in mind that these are just some thoughts from a care-giver (and not a medical professional!)

Jason

Re: Need guidance

Jason - Thanks very much for your suggestions - I thought I probably should get a second opinion and I guess I just needed someone to confirm it should be done -
I'll set up an appointment at Mayo as you suggested - Again, thanks for your input -

Re: Need guidance

Carl,

Glad to hear that Lynn's doc has changed her to Losartan and my fingers are crossed for this to work well for her. It is good to hear as well that the doc read the info that you provided and did not have a closed mind about things and made the change straight away. A small step on the road to recovery indeed my friend but good things can start with small steps. Please let us know how things go with this and know that I am thinking of you and Lynn.

My very best wishes to you and Lynn,

Gavin

Any advice or comments I give are based on personal experiences and knowledge and are my opinions only, they are not to be substituted for professional medical advice. Please seek professional advice from a qualified doctor or medical professional.