update featuring herceptin and lapatinib

[Voxx66]

Last update I had just had my ascites drained and the liquid biopsy drawn.

The ascites only 3 weeks later are as bad or worse than before. I intend on having it drained this week again.

The liquid biopsy revealed 9 alterations 2 of which are supposedly good targets. The mutations are ERBB2 and FGFR2. My doctor wants to try Herceptin (a breast cancer drug) along with lapatinib (a drug that is hepatotoxic and seems like a no brainer to refuse) He claims Herceptin has few side effects but that is not what I am reading on the web.

Has anyone tried Herceptin and can comment on side effects?

Next my bloodwork is bad. My liver numbers are climbing and I have had really high creatinine levels. Had tests last week and no cancer or blockage in kidneys. The thought is that the ascites is causing it.


Anyway - there is probably more but I haven't slept so that will have to wait until later.

V

[midlifemom]

Just a thought - perhaps you could look at a breast cancer forum for the herceptin side effects.

Thanks for the update.

[GrouseMan]

Voxx - This combination might be a winner if Her2/Neu (ErbB2) is driving these ascites. This sounds very similar to the combination use of Cetuximab (Erbitux), and Panitumumab (Vectibix) for CRC that recently is finding some interest for people that after initially using Cetuximab developed resistance (maybe T790M mutation). Seems the two together seems to re-regulate the EGFr pathway again. Of course I am biased and I think you would likely benefit from Dacomitinib which inhibits EGFr, ErbB2 (Her2/Neu), and ErbB4 as well as the T790M, gatekeeper mutation, present in up to 50% of tumors that have acquired resistant to first-generation EGFr inhibitors. http://www.ncbi.nlm.nih.gov/pubmed/23294134 Your oncologist may cite the failure of Dacomitinib in NSCL cancer but I believe it failed as the trial was poorly designed.

The rash can be managed, its uncomfortable, but in clinical testing with CI-1033 (another early EGFR inhibitor) we used Benadryl to help manage the rash. I think now there are good protocols for getting control of this rash issue.

A drug furthest along in the clinic (Phase III) that might target your FGFR2 target is Nintedanib (BIBF 1120). Its a Pan Tyrosine Kinase inhibitor that inhibits most of the VEGFr/PDGFr/FGFr isoforms. Think of this as being a super Avastin sort of small molecule rather than an Antibody. Unfortunately side effects from a drug like this one often can be pretty hard to take I believe. For a discussion in Wikipeda see :https://en.wikipedia.org/wiki/Nintedanib

Good Luck.

GrouseMan

[Nik Colon]

Thanks for the update, sorry for the issues, best wishes

[DarknessEmbraced]

Thanks for the update. Sorry you're having such a hard time!*hugs*

[pfCml73183]

That ascites is horrible. I remember Pete having a horrible time walking in Manhattan. He was having a hard time breathing and it was so difficult on him. He also had the lung mets too as well : (
I sure hope you can get them drained again soon, that is such a burden to carry around with all you have happening right now.
Have you any more feelings or opinions about the new drug being offered to you?
Celeste

[DK37]

Depends on which ERBB2 (aka HER2) mutation you have and if it is driving your tumors but here is a brand new pre-clinical paper that just came out this month which shows treating the ERBB2 S310F, L755S, V777L, V842I, and L866M mutations with Herceptin (trastuzumab) + either neratinib or lapatinib. This co-therapy worked well in "patient derived xenograft" animal models.

http://cancerdiscovery.aacrjournals.org ... 2.abstract
(abstract's "significance" from the journal is pasted below)

Good luck!
-DK

Significance: HER2 activating mutations cause EGFR antibody resistance in colorectal cell lines, and PDXs with HER2 mutations show durable tumor regression when treated with dual HER2-targeted therapy. These data provide a strong preclinical rationale for clinical trials targeting HER2 activating mutations in metastatic colorectal cancer. Cancer Discov; 5(8); 832–41. ©2015 AACR

[stu]

Well thankfully some awesome posters have the science covered so it just leaves me to send good wishes and sincerely hope this picks up for you soon. Obviously I had a whole list of current research to bring to the table but they got there first. Hee.
Seriously though that sounds rough and I hope for a speedy response.
I just love the knowledge that people are willing to share here.
Kind regards
Stu

[CRguy]

Hey buddy,
I am with stu … glad GrouseMan and DK37 got here with some timely news and info !

Keep ON keeping' On bro'
stayin' strong on the Journey

Harmony
CR

[GrouseMan]

DK, thanks for the HER2 reference. Quite interesting. Wish I could test Dacomitanib against these mutations listed. So many ideas no lab availability

GrouseMan

[DK37]

DK, thanks for the HER2 reference. Quite interesting. Wish I could test Dacomitanib against these mutations listed. So many ideas no lab availability

GrouseMan

I hear you GrouseMan... I'm sure Dacomitanib would work fine in these same studies, I feel your frustration...
It was a funny twist of fate. I had just seen that paper 2 days ago & gave a copy to my oncologist - so it was in the front of my mind when I saw this post today-

-DK