Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

ASCO last week talked about a promising new tx for her2 , w/ brain mets. a genetic drug - ON380 ( sp. ? ) added to kadcyla. phase I had good results in 8 out of 8 pts who got this combo.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Carol is still doing fine. She now gets the IT and IV treatment of herceptin every 3 weeks, 150mg IT with hydrocortisone, and 6mg per kilo IV. No new mets developed and older ones under control. Hope this ONT-380 with TDM1 gets approval soon. A pill would be much better than IT, with the risks it has, especially with the big risk of meningitis.

It is nearly 5 years now since the 2cm brain tumor was treated with local radio therapy, and 4 years since it come back into several spots again treated locally! It is nearly 3 and a half years since we started IT herceptin.

So those of you fighting brain mets do not give up.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Thanks so much for the update on Carol.
Somehow I have missed ONT-380.
Should we start a new thread and "stick" it for this possibility?

A pill sounds grand. My nephew's wife has just been in quarantine for meningitis and it has been very tough for her as she is a young mother. (She does not have cancer, so I do not know how she got the disease.)

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Here are some questions that aren't addressed here:

Has anyone who has had IT Herceptin treatment ever stopped it due to presumed disease eradication?

In the absence of tests confirming disease advancement, has IT therapy ever been done to prevent disease progression in previously treated HER2 brain mets patients?

What are the worst side effects seen with IT Herceptin? Have patients had to stop being treated due to issues?

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Good questions, here are some answers:

Has anyone who has had IT Herceptin
treatment ever stopped it due to presumed disease eradication?
Not sure on this point. Nina was told they would not stop because they do not know if there is any way to determine if there is full remission or not. Insurance continues to pay for it because they also do not know when to stop either.

In the absence of tests confirming disease advancement, has IT therapy ever been done to prevent disease progression in previously treated HER2 brain mets patients?
Nina had Band radiation, Gamma Knife, and Tykerb/Xeloda before IT.

What are the worst side effects seen with IT Herceptin? Have
patients had to stop being treated due to issues?
There is a risk of stroke if the does is too high at the start and some have had headaches. Nine has not had any issues.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Does anyone know if more than 150mg of IT herceptin per week was ever used, since my doctor wants to know, since carol's brain mets are not gone with 150mg IT per 10/11 days.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Yesterday we did the first IT herceptin at 200mg. All went well, no side effects.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Hi,

Just saw your question. I'm glad to hear 200 mg was well-tolerated. The only other high dosage I heard of was in the IT Herceptin trial that is ongoing. The dosage I heard of was 80 mg twice a week, which is somewhat comparable to 200 mg in a week.

-A

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

In the NYC Metro area, I know for a fact that Dr. Joachim Baehring at the Yale Smilow Cancer Hospital in New Haven, CT treats leptomeningeal disease with an IT Herceptin regimen. 50 mg or 100 mg IT Herceptin is administered with 50 mg theradopa (cytotoxic agent) on a weekly basis through an Ommaya or lumbar resorvoir. There are minimal side effects at the 100 mg dosage, as in lethargy the day after administration, that's it. I've seen it have brilliant effects.

That being said, I still think radiotherapy is necessary in known areas of disease in the brain and spine. If it was not done already, though, you may want to discuss doing the IT Herceptin first if the tumors are not compromising critical brain stem areas (e.g. controlling breathing) or are causing paralysis.

IT Herceptin has proven to be excellent in prolonging the life of LM patients. I've read case reports of patients pulling 2-4 years until the disease stopped responding. That is the greatest danger with IT Herceptin. Once the tumor mutates to lose the HER2 ligand, the options are limited just to cytotoxic therapies and radiotherapy. IT Methothrexate is allegedly well tolerated (I have no personal experience to attest to that) but controls disease progression for maybe 4-6 months.

So, combination therapies could be a good option. I am personally in favor of IT Herceptin 100 mg every week as a base therapy coupled with the pulsile Tykerb treatment which was made reference to on this forum (protocol of biweekly lapatinib administered orally with a loading dose of 5000 mg /20 pills/ on Day 1, 6250 mg on Day 4 /25 pills/ and 7500 mg on Day 8 /30 pills/ administered every four days therafter). That way, you have two HER2 immunotherapies attacking the tumor.

For those willing to also integrate some additional therapies, CBD oil 2 ml twice a day should be given, Curcumin extract, Rei-Shi mushroom extract, and essential element supplementation as necessary based on bloodwork (especially K, Mg, and Ca if you are using Tykerb in combination with IT Herceptin). Care should also be taken to enrich your diet with tumeric, ginger, garlic, sweet potatoes, habaniero peppers, and eliminate any and all dairy products and oils, plant or animal based.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Hi What is theradopa? can not find this drug. What is CBD oil ?

Iam living in arizona they say IT methotrexate is very hard on the body. Use is for Valley fever.

Peace and prayers Darita

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

I apologize, the cytotoxic compliment to IT Herceptin used in Yale is IT thiotepa, 50 mg weekly. It is similar to other combination therapies I've read about in the literature, specifically a combination of IT Herceptin and IT methothrexate (100 mg/wk and 25 mg/wk, respectively). The reservation, of course, with a cytotoxic compliment is that it is cytotoxic. Both methothrexate and thiotepa stay around in the meninges and in the body for a long time, and have documented side effects such as arachnoiditis and some neurodegeneration. That being said, they were valuable compliments to IT Herceptin. Using methothrexate or thiotepa in monotherapy stops working after 5-6 months, in some cases longer, simply because you are attacking the tumor with just one agent, rather than a targeted agent and a cytotoxic agent. Other cytotoxic agents that I've encountered in literature was etoposide 1 mg/wk, topotecan, as was mentioned earlier in this thread, and Xeloda as a systemic compliment that has some CNS penetration.

CBD oil is cannabidol oil (hemp oil). While I am cautious about people making outlandish claims that it is a panacea for neoplasms of all kind, real research suggests that brain and breast origin tumors have endocannabinoid receptors that could be targets for at least few of the many cannabidols found in hemp oil. Plus, anecdotal and formal evidence suggests it potentiates response to pain meds, potentially allowing patients to take less pain meds with the same effect. Generally, these compounds also have an anti-inflammatory effect. If it doesn't have THC, it is not psychoactive and in my book, doesn't hurt. The dosage I've seen is 25 mg/day, which in some blends translates to 2 ml of oil a day.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

I wanted to add also this. In LM patients, CSF flow abnormalities are common. Circulating cancer cells/emboli obstruct the drainage of the meninges and hydrocephalus can develop, with all of its associated clinical manifestations. Although as the CSF clears of cytologically perceptible tumor cells, one would expect that the hydrocephalus subsides or normalizes. During this time, then, extraction of CSF via the Ommaya reservoir should be undertaken, as much as 35 ml per IT administration, until there is MRI confirmed resolution of the hydrocephalus.

If possible, a CSF flow obstruction study should be conducted to make sure that the neuroaxis is accessible to IT administered agents. If there is a tumor blocking CSF flow, say in the lumbar spine, the area below will develop multiple metastasis since it is not being treated, unless systemic therapy is penetrating the BBB in the obstructed area. Such a study, radionuclide ventriculography, also helps to identify gross masses requiring radiotherapy. IT Herceptin or any other cytotoxic agent has limited effect on gross masses, and spot radiation should be applied to the known tumors.

Finally, salvage therapy. What happens when methothrexate stops working? Or Herceptin? Thiotepa is seen as a salvage therapy for when methotrexate fails, but can also be used as a first line therapy, as is done in Yale. In the case of Herceptin, that is more frightening since it may suggest that the tumor underwent clonal selection to lose its HER2 ligand. Tykerb was suggested as a second line salvage therapy in cases of suspected desensitization to Herceptin, combined with Xeloda - the issue, however, being that you need high doses of Tykerb to push a therapeutic dosage into the brain from the bloodstream. I've read a case report in which etoposide 1 mg/wk was used as salvage therapy in the case of methothrexate failure. From what I read in this thread, some MO's may also seek to up the dosage of IT Herceptin to 150 mg or 200 mg/wk, suggesting that the tumor in such cases has simply been downregulated and did not in fact lose the HER2 ligand. A combination of IT Herceptin and Perjeta is also something I think would improve outcomes in the case of IT Herceptin monotherapy failure, but that is just my opinion. For the sake of my Mother, I want to see who would do such a protocol of treatment. Are there others? I've seen IT interferon as a third line therapy in an article, but that is its own can of worms and has probably only limited effect.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Sorry to jump on the thread. Does anyone know if IT Herceptin reaches the Dura layer?

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Carol is still with mets
7 months ago she was locally irradiated for 3 mets measuring 12,12, and 7 mm. She continued doing IT herceptin at 250mg every 10 or 11 days till today.

In the first 3 months the mets shrunk to 6,7, and 3 mm. But an MRI last week showed that these have grown up to 13,13 and 8mm.

So today is the last IT herceptin that she is doing. We will start 1250mg/day tykerb and 130mg taxol per week as from today. She can still walk with some help, steroids are at 1mg/day, and still taking IV herceptin at 6mg/kilo.

We will do 6 weeks like this and then do another MRI.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Hi Mario,

Is Carol able to have Gamma Knife for the lesions? Are they deep brain or leptomengenial?

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

They are deep brain, but she cannot do a gamma knife

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

Hello Mario,

Sorry to learn of the growth you described. Maybe slapping those mets with something new will send them slinking away.
I hope her quality of life is well enough after all this time of treatment.

I would like to know what side effects (if any) you could attribute to the IT Herceptin.

All the very best to you both.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

intrathecal herceptin had no side effects even at a dose of 250mg. we did this over 100 times in the past 4.5 years

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

MRI of 2 weeks ago show that the three tumors have shrunk to half, showing that taxol and lapatinib is working. However she is having complications with blood parameters and is in hospital to be controlled, having had very low blood presure 50/20, very high heart beat, 150 while sleeping, rapid breathing, low spo2 needed oxygen, low red bc, low white bc, low platelets, chest infection, near kidney failure, large fluctatuations in potassium, calcium, sodium and chlorides.
However she is settling and is now taking a blood transfusion.

Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase
 

So sorry Carol is so ill. That must be really hard for you both.

Sending warm wishes and hopeful thoughts.

Amy