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Old 06-10-2015, 10:52 AM   #201
phil
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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.
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Old 09-25-2015, 11:04 AM   #202
marvass
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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.
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Old 09-25-2015, 06:53 PM   #203
StephN
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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.)
__________________
"When I hear music, I fear no danger. I am invulnerable. I see no foe. I am related to the earliest times, and to the latest." H.D. Thoreau
Live in the moment.

MY STORY SO FAR ~~~~
Found suspicious lump 9/2000
Lumpectomy, then node dissection and port placement
Stage IIB, 8 pos nodes of 18, Grade 3, ER & PR -
Adriamycin 12 weekly, taxotere 4 rounds
36 rads - very little burning
3 mos after rads liver full of tumors, Stage IV Jan 2002, one spot on sternum
Weekly Taxol, Navelbine, Herceptin for 27 rounds to NED!
2003 & 2004 no active disease - 3 weekly Herceptin + Zometa
Jan 2005 two mets to brain - Gamma Knife on Jan 18
All clear until treated cerebellum spot showing activity on Jan 2006 brain MRI & brain PET
Brain surgery on Feb 9, 2006 - no cancer, 100% radiation necrosis - tumor was still dying
Continue as NED while on Herceptin & quarterly Zometa
Fall-2006 - off Zometa - watching one small brain spot (scar?)
2007 - spot/scar in brain stable - finished anticoagulation therapy for clot along my port-a-catheter - 3 angioplasties to unblock vena cava
2008 - Brain and body still NED! Port removed and scans in Dec.
Dec 2008 - stop Herceptin - Vaccine Trial at U of W begun in Oct. of 2011
STILL NED everywhere in Feb 2014 - on wing & prayer
7/14 - Started twice yearly Zometa for my bones
Jan. 2015 checkup still shows NED
2015 Neuropathy in feet - otherwise all OK - still NED.
Same news for 2016 and all of 2017.
Nov of 2017 - had small skin cancer removed from my face. Will have Zometa end of Jan. 2018.
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Old 10-01-2015, 07:01 AM   #204
agness
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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?
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
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Old 10-01-2015, 08:56 AM   #205
Rolepaul
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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.
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Old 03-10-2016, 05:27 AM   #206
marvass
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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.
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Old 03-11-2016, 10:50 AM   #207
marvass
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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.
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Old 05-11-2016, 09:20 AM   #208
agness
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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
__________________
  • Dx 2/14 3b HER2+/HR- left breast, left axilla, internal mammary node (behind breast bone). Neoadjuvant TCHP 3/14-7/2. PCR 8/14 LX and SND. 10/21-12/9 Proton therapy to chest wall.
  • Dx 7/20/15 cerebellar met 3.5x5cm HER2+/HR-/GATA3+ 7/23/15 Craniotomy.
  • 7/29/15 bone scan clear. 8/3/15 PET clean scan. LINAC SRS (5 fractions) Sept 2015. 9/17/15 CSF NED, 9/24/15 CSF NED, 11/2/15 CSF NED.
  • 10/27/15 atypical uptake in right cerebellum - inflammation?
  • 12/1/15 Leptomeningeal dx. Starting IT Herceptin.
  • 1/16 - 16 fractions of tomotherapy to cerebellum, break of IT Herceptin during rads, resume at 100 mg weekly
  • 3/2016 - stable scan
  • 5/2016 stable scan
  • 7/2016 pseudoprogression?
  • 9/2016 more LM, start new chemo protocol and IV therapy treatment with HBOT
  • 11/2016 Cyberknife to temporal lobe, HBOT just prior
  • 12/2016 - lesions starting to show shrinkage
  • 8/2017 - Stable since Dec 2016. Temporal lobe lesion gone.
  • Using TCM, naturopathic oncology, physical therapy, chiro, massage, medical qigong, and energetic healing modalities in tandem. Stops at nothing.
  • Mother of 2 boys - ages 7 and 10 (8/2017) and a lovely partner with lots to live for.
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Old 05-21-2016, 10:23 PM   #209
YoungMD
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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.
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Old 05-22-2016, 09:26 PM   #210
dchips1
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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
__________________
dx 1/06 IDC 2cm 38 at dx
2/06 L mast nodes 3/9+ SNB neg ER-/Pr - her2 + Stg 4 liver/pelvis
3/06-9/06Taxol/Carbo/zometa/Herceptin
3/07 6 brain mets WBR down to c-2
4/07 osteonecrosis jaw
1/08 mri new 9mm lesion right lower side
2/08 gamma knife 1 lesion 11/08 regamma
10/09 latent rad necrosis to brain met,
1/20/10 crani: lesion necrosis w active cells continue her add tykerb
1/11 NED just Ingrown toenail! YEAH GOD
8/11 Tykerb, herceptin weekly, elevated her2 levels, negative scans
oct -march 11 new neuro deficits lower legs
3/12 2 spinal metsTykerb, Herceptin
04/12 4050cGY rads T 2-4 & T7-9
5/12 Brain,cervical lumbar clear/thoracic slight decrease
10/12 t 2-4 shrunk t-9 grew start Xeloda, 02/13 stop xeloda,5/13 on metformin, decadron, Tykerb, iv and IT herceptin 5/30/13 total #11 #2 of 80mg dose weekly.
9/13 100mg of IT her, IV hern, 750 mg tykerb, 3mg dec.
last Mri T--3 SHRUNK t7-9 shrunk no edema. Left shift in CBC bone marrow BX negative.
10/13 Ct has shown Double left ureters with stones/cysts in them, after 3 births and lots and U/S iit takes cancer to figure out you have 2 smaller ureters going into 1 kidney!
12/13 Mri brain no new lesions, cervical and lumbar arthritis.
Tspine lesion at T3 stable, T 7-9 GROWTH lots of pain

1/29/14 HIHO HIHO its off to Neuro surgery I go





Life is Good when you wake up in the morning and take a breath and know that God has given me another day.


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Old 05-23-2016, 11:55 AM   #211
YoungMD
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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.
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Old 05-23-2016, 12:56 PM   #212
YoungMD
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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.
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Old 05-31-2016, 08:45 AM   #213
Freakzilla
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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?
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Old 11-17-2016, 06:28 AM   #214
marvass
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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.
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Old 11-17-2016, 12:56 PM   #215
Ramsay_Bolton
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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?
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Old 11-17-2016, 01:34 PM   #216
marvass
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Re: Intrathecal (IT) Herceptin (Trastuzumab) for brain mets (Leptomeningeal Metastase

They are deep brain, but she cannot do a gamma knife
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Old 11-25-2016, 01:51 PM   #217
StephN
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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.
__________________
"When I hear music, I fear no danger. I am invulnerable. I see no foe. I am related to the earliest times, and to the latest." H.D. Thoreau
Live in the moment.

MY STORY SO FAR ~~~~
Found suspicious lump 9/2000
Lumpectomy, then node dissection and port placement
Stage IIB, 8 pos nodes of 18, Grade 3, ER & PR -
Adriamycin 12 weekly, taxotere 4 rounds
36 rads - very little burning
3 mos after rads liver full of tumors, Stage IV Jan 2002, one spot on sternum
Weekly Taxol, Navelbine, Herceptin for 27 rounds to NED!
2003 & 2004 no active disease - 3 weekly Herceptin + Zometa
Jan 2005 two mets to brain - Gamma Knife on Jan 18
All clear until treated cerebellum spot showing activity on Jan 2006 brain MRI & brain PET
Brain surgery on Feb 9, 2006 - no cancer, 100% radiation necrosis - tumor was still dying
Continue as NED while on Herceptin & quarterly Zometa
Fall-2006 - off Zometa - watching one small brain spot (scar?)
2007 - spot/scar in brain stable - finished anticoagulation therapy for clot along my port-a-catheter - 3 angioplasties to unblock vena cava
2008 - Brain and body still NED! Port removed and scans in Dec.
Dec 2008 - stop Herceptin - Vaccine Trial at U of W begun in Oct. of 2011
STILL NED everywhere in Feb 2014 - on wing & prayer
7/14 - Started twice yearly Zometa for my bones
Jan. 2015 checkup still shows NED
2015 Neuropathy in feet - otherwise all OK - still NED.
Same news for 2016 and all of 2017.
Nov of 2017 - had small skin cancer removed from my face. Will have Zometa end of Jan. 2018.
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Old 12-31-2016, 01:08 PM   #218
marvass
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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
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Old 01-23-2017, 08:30 AM   #219
marvass
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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.
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Old 01-23-2017, 04:44 PM   #220
Mtngrl
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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
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