? for Lani and any other propeller heads...lol

[Tom]

I have been wondering about something for some time now. As many of you know, ny Mom has had no conventional chemotherapy of any kind, receiving only Herceptin and radiation therapy. Now, the Herceptin has been temporarily stopped due to a precipitous drop in her LVEF (69%->49% over three month period).

Considering that the primary action of Herceptin is to block the HER2 oncoprotein receptor site on the cell surface, it seems to me that the existing HER2+ cells wil be free to resume growing and dividing when there is a lack of the monoclonal antibody to block those receptor sites.

I understand that one possible side benefit of Herceptin is to trigger the immune system to attack and kill the HER2+ cells, but this has not been proven. Therefore, I might assume that since Mom has had no other chemotherapy that would normally kill off remaining malignant cells, these cells should be a matter of serious concern.

Simply put, how worried should I be that Mom get back to Herceptin infusions as quickly as possible? A second question would be whether she falls into any criteria that would allow her to participate in the EAP for Tykerb. I am going to call GSK tomorrow and hopefully get the answer to the last question soon.

Tom

[Lani]

please read my post regarding why they don't test bone marrows on newly diagnosed patients and then again after treatment.

I do believe in the stem cell theory of breast cancer--that those cells in the bone marrow are dormant and divide only once in a blue moon until the environment is right for recurrence. That is why those cells in the bone marrow are not affected by cytotoxic chemotherapy.

I like to think that those stem cells or progenitor cells have her2 on the surface and that herceptin can clear them from the bone marrow. I read today an interesting article showing it cleared tumor cells from the bone marrow of metastatic breast cancer patients when chemotherapy hadn't.

Another theory is that herceptin can't work as well to stimulate the immune system to kill the her2neu cancer cells if there isn't some antigen around to acquaint the immune system with. I like to think that radiation therapy creates enough antigen for the immune system to recognize without necessarily having had chemotherapy.

So optimistically one can HOPE that the herceptin and radiation therapy alone might have cleared any cells in the bone marrow, but this is sheer speculation. I wish bone marrow biopsies before and after the main avenues of treatment to follow the results of treatment would become routine. We might be able to see whether those pesky stem cells that behave like "mold spores" in your shower were merely hiding in dormancy or truly eliminated.

All of what I have been speculating about is unknown as clinical trials looking to see if less does just as well as more are almost never done. Look how long it has taken for the accelerated partial breast clinical trials to get done and how few there are (no drug companies paying for them among other things)

The usual rationale given regarding why they do not try less is because they could get sued for not giving people the best known treatment (therefore they just add the new treatment on top of it and see if the results improve).

The group they would be most inclined to do less for , older patients like your mother--make bad candidates for clinical trials as they are likely to die of other causes before results are known regarding the subject matter of the trial.

From what I understand, tykerb will be allowed only in metastatic cases to start with. How long it will take before they use it in the adjuvant setting is unknown. Perhaps some kind oncologist would "complete" the one year of adjuvant antiher2 therapy with tykerb once it is available to be used off-label. If you hear differently, please let us all know right away!

Have never been called a propeller-head before. Is that why I am a "dizzy
dame"?

[chrisy]

Dear Tom,
Sorry, I'm not a propeller-head but I'm interested to hear more on this question, too.
In your mom's case, shame on me for not remembering this, but I thought your mom had some positive nodes but NOT metastatic disease? If this is so, Lani is correct in that the approval is for metastatic disease. BUT since your mom's oncologist mentioned Tykerb to you (after subliminally processing your suggestions about this!), perhaps that's a good indicator that he would be willing to try it for your Mom.
In the meantime, take heart in the "good" numbers that you got on the recent blood tests...it may mean you have a little breathing room until Mom's LVEF rebounds.

I wish my brain was propelled, instead of just my mouth...lol

[Becky]

Another way to create the antigen reaction is to use GM-CSF instead of G-CSF during chemotherapy. You can do this in hope to create a self vacinnation system so that later, Herceptin can work even better. I had a huge fight on my hands over this but won the battle, prior to beginning chemo to receive CM-CSF (brand name Leukine) vs Neulasta. I felt it could give me an edge since adjuvant Herceptin was not available to me then (began receiving 4 months after my last chemo therapy and about 2 months after completion of rads - of which I paid for 5 doses of Leukine on my own starting with my last boost).


I am hoping that Herceptin has cleared any bc stem cells from my bone marrow (if there were any there) or that the dendritic effect of the Leukine helped me.

Kindest regards

Becky

[Christine]

Tom
It is important to note the time the EF test is given after taking the last dose of Herceptin. I have found that taking an ECHO shows the true EF if you wait 2-3 weeks after herceptin infusion. I don't recall how old your mom is, but being causious is at her best interest. Also, getting her indusions every 3 wks works well. HERCEPTIN HAS THE ABILITY TO WORK FOR OVER A MONTH. mONTHLY INFUSIONS MAY BE SUGGESTED TO HER oNC TO START EASILY . aLSO CHECK THE DOSE FOR HER WEIGHT;SHE MAY HAVE LOST WT AND NEEDS HERCEPTIN DOSE ADJUSTMENT.
Tykerb may be an option, but the FDA is still evaluating it for safety etc.etc.
I do believe tykerb ca work, but know nothing about side effects.
Hope this helps Hugs to u & mom
tOM, GET HER ANOTHER ECHO a month after Herceptin.

[heblaj01]

Tom,
You probably remember the Finnish study showing that a short 9 week Herceptin treatment had lasting effect. So a relatively brief interruption may not have serious consequences. The other case to recall is that of Gina with her repeated ON/OFF treatment cycles.
When your mother resumes Herceptin or goes eventually to Tykerb, it may still be usefull to go on with Herceptin even if resistance sets in (hopefully not so). As you may recall several oncs have commented that Herceptin is still beneficial after progression at least in some instances (Ref.2). I do not know not for sure why this is so but one of the reasons may be its multiple antiangiogenesis modes of action that have been discovered in the past:
Ref. 1
http://www.oncolink.com/resources/article.cfm?c=3&s=8&ss=23&id=8198&month=03&year=2002 (http://www.oncolink.com/resources/article.cfm?c=3&s=8&ss=23&id=8198&month=03&year=2002)

Herceptin reduces the expression of at least three angiogenesis-related genes and upregulates an anti-angiogenic factor

Ref.2
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12820439&dopt=Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12820439&dopt=Abstract)
The effect of trastuzumab/docatexel combination on breast cancer angiogenesis: dichotomus effect predictable by the HIFI alpha/VEGF pre-treatment status?

This, on the surface, but not in fact, looks analogous to the remaining antiangiogenesis mode of action of low dose chemo after cytotoxic high doses have become useless.

However one of the uncertainties of both Herceptin or Tykerb prolonged treatments is the possible shift, in some cases, from HER+ to ER+

[Tom]

I'm sorry I have not replied sooner, but I lost a dear friend to congestive heart failure recently and have been tied up with her family as they struggle through their loss. I was glad to get commentary from all you guys, as this has been weighing on me as Mom's time without Herceptin has passed. Mom should be getitng another MUGA this week or beginning of next, and we will make decisions about her treatment then.

Remember that Mom's oncs were in disagreement about the existence of mets for a while, and I try not to take any chances. She did not have definitive mets at the time of her first and second surgeries, but did have extensive axillary node disease (12 of 20+) following her axillary dissection. It was always that information that I used in order to convince her oncs to proceed aggressively with treatment, reminding them that she would most likely not be able to tolerate any conventional chemotherapy, as she is now 82.

I contacted GSK, and requested their Tykerb EAP application package, which I will deliver to her onc as soon as I get it. The contact person told me that the EAP process involves the use of Tykerb along with Xeloda. I do not believe that there is any way they will bend the rules and allow the Tykerb to be given alone or with Herceptin rather than Xeloda. She reminded me that Tykerb may be approved as soon as the end of this year, and that oncs should basically be able to use it as they wish.

I believe that if Mom's MUGA numbers are OK, I will ask that she begin Herceptin infusion again immediately, and wait to see how the Tykerb approval process plays out in the meantime. Christine's LVEF testing timing is also of great importance.

The onc has also agreed to have more imaging studies done shortly in order to stay on top of the situation. This onc has been a Godsend to us, and is cheerful and willing to consider whatever treatment options I suggest, but is also willing to tell me if I am going down the wrong road. That attitude is invaluable, and is harder to find than a half-eaten chocolate eclair in my fridge.

And I should mention for the record, that propeller heads are the object of my desire, and the term is one of endearment when I use it (Lani, you go girl). I yearn to some day have a wife that would rather read a good science article than watch a soap opera or Desperate Housewives...lol. The only thing I want my wife to be desperate about is seeing that the fridge is never empty. I don't even want her to cook, as long as she doesn't mind watching me eat. I always think better when I have a mouthful of something yummy. So if there are any single propeller heads out there that love to eat too, please send a resume.

All kidding aside, I really do appreciate all of the headache promoting reading that you guys do in order to provide us with the latest treatment options. It's not always easy to plow through some of these abstracts, stopping every 5 minutes to look up medical terminology. Keep up the good work and thanks again to all.

Sincerely,
Tom

[heblaj01]

Tom,

I forgot to mention in m previous post the regimen of low dose Heceptin (100mg/week) + Vinorelbine(28mg/week, 3 weeks ON ,1 week OFF) prescribed for a 90 year old lady in my family.
This may be less harmfull for the heart.
Initially only Herceptin was prescribed but after 2 months markers started to rise again afyter having dropped 40%
The recent addition of Vinorelbine has started (after 8 weeks) to reverse the trend in markers as well as reducing the size of the recurrent primary tumour & ending back & neck pain.
Side effects of Navelbine have so far been mild & temporary: upper gastric pain, back pain, moderate constipation all happening in the first 2-3 days after infusion.
Platelets & neutrophils have moderately gone up & down each week but well within normal limits.

[Tom]

Thank you Heblaj for that last not of information. It is the first time I have had any first hand input with respect to the treatment of elderly or frail women with breast cancer. There isn't much out there about it, and it has always been difficult to imagine any options using snything but Herceptin. I appreciate you writing.

Sincerely,
Tom

[Lani]

I think I posted a trial of low dose metronomic cyclophosphamide and Herceptin for you a while back. I thought you would keep in your back pocket should your mother recur. It is out of Europe, but all drugs are approved in US and a "non-square" oncologist could easily put such a treatment program together ie, one who doesn't only follow the cookbook.

If you can't find it, let me know.

[Tom]

Lani,

I did read that information from you a while ago, and I save most of your posts on my hard drive for quick access. I have investigated metromic dosing of several chemotherapy agents. My earlier comment was meant to say that I had not heard any first-hand accounts by people who had friends or relatives that were elderly. I should have been more clear. I put a lot of faith in personal stories when it comes to cancer treatment options. I know that hard clinical research is more reliable, but real-life accounts by flesh-covered humans always hit home harder for me.

Tom