Intrathecal Herceptin/Topotecan for Leptomeningeal Disease

[Rolepaul]

My wife, Nina, was found to have Leptomeningeal Disease in the spine with too many spots to count and three active leasions in the brain Dec 15, 2011. With hard work by many people, she had ten rads of her back and spine, and started weekly 40 mg Intrathecal (IT) Herceptin on 1/12/12. 2/3/12 the dose was increased to 80 mg and 0.4 mg topotecan twice per week. IV Herceptin was added with Navelbine. Not many people thought she would be alive at the end of February. Here it is middle of May 2012 and she is celebrating Mother's Day after her mother's birthday last week. She is down to Topotecan once per week, and we are looking at getting down to Topotecan once every two weeks, as well as the IT Herceptin. The IV Herceptin and IV Naavelbine we are looking at also once every two weeks. Insurance coverage has been good from anthem Blue Cross Blue Shield, MD Anderson has been supportive of patient suggestions, and Genentech has offered to help with putting the treatment plan into more clinical trials. I hope that everyone that is having brain mets can get this information and maybe get similar results. By the way, she has been driving, walking five miles per day, Yoga, Kindle, computer searching, and looks great since the initial diagnosis. She has tightness in the lower back to the knees that we are working on. Inspiration of others is the best way to feel good about yourself.

[dchips1]

I am so glad she is doing so well! where is she being treated, did she have an ommaya reservoir implanted?

Praying for my Mri in 2 weeks to look good with my 2 mets to be gone as well.

Darita

[Rolepaul]

Darita,

YOur progression is very similar to Nina's! She is being treated at MD Anderson in Houston Texas. I heard UCLA might also be treating patients with IT Herceptin. She is using an ommaya reservoir. We are trying to get the topotecan reduced because I heard that only Herceptin will not cause meningitis long term. Good luck to you. MRI for brain and spine 5/30.

Paul

[StephN]

Hello RP -
You and your Nina have an amazing story. She is a true success to keep beating back her prognosis.

This is the support group where your story is so very much appreciated. Over the years we have had a few members try the intrathecal method and a couple of the first patients were over 8 years ago right on the forefront of that treatment.

Now there are new and better drugs to insert. Nina is proof of that!

Please keep us updated on the reduction of her treating drugs and how Nina is doing generally.

[Rolepaul]

Nina gets down at times, but is now looking to go back to giving therapeutic massages or being a clinic RN. The IT Herceptin with Methotrexate was a good first thought, but the darn stuff irritated the brain surface and caused some problems. One of the contacts on this site had her daughter have an issue with insurance that got my attention and the doctor transitioned to the topotecan as that had previously been run at MD Anderson with okay results. Piggybacking the two together was the secret. I wish it had been done five years ago and saved hundreds, if not thousands, of lives. We keep spreading the information to help others. Nina is getting ready for her 53rd birthday in July and just spent Mother's Day in Washington DC with our son.

Success is not measured by the number of steps you take to your target, but by the number of ones that are past your target. We left the target from the initial assessment from Xmas 2011 back three months ago, and we are not going to look over our shoulders again.

Paul and Nina

[potra]

Dear Paul and Nina, delighted to hear your story! Gives me hope. I've asked for a second opinion at MDAnderson, Madrid.

[Rolepaul]

Potra,

Have them contact the main center in Houston Texas. Dr. Loghin is the neurooncologist and Dr. Melhem-Bertrandt is the breast oncologist. This was a compassionate care treatment, but I think they want to get a full study going. There are a tremendous number of patients and it was noted in 2007 that this was going to occur with Herceptin and brain involvement. 30% of all HER patients have your situation, and in the past there was not a good method to treat it. This appears to work for a couple of patients, now it is time for more women to be treated with this. It is not inexpensive, but it has a good chance of working based on the results I have seen with Nina and with others that are not in major publications. I hope this is a road map for many more patients that are on this blog.

[potra]

thank you very much Paul, I have a consultation with them -next week-I'll let you know how it goes. I knew about the stats for Her2 patients and was "prepared"-also I'm a vet so it's not as scary as it might be for others, makes me very proactive-something they aren't used to here.

[Rolepaul]

Porta,
Good luck next week. We are at MD andsrson Houston. Nina is only one in this regimen. Keep pushing as she is doing really well. Monitor spinal prptein and glucose for dffectivendss. Mlre Monday when I am back in Raldigh.
Paul

[potra]

Can't thank you enough...my love to nina, Miriam

[alexandra1]

Paul did nina have breast cancer that metastasized ?

[Lani]

Hot off the "press"

Reading the abstracts for the upcoming ASCO annual meeting I found this:

2015 Poster Discussion Session (Board #3), Fri, 1:00 PM-5:00 PM and 4:30 PM-5:30 PM
Intraventricular (IVe) topotecan for women with neoplastic meningitis (NM) asso- ciated with 􏰑responsive􏰑 malignancies.
Kurt A. Jaeckle, S. Keith Anderson, Anna Willson, Gerardo Colon-Otero, Tejal Amar Patel, Edith A. Perez; Mayo Clinic, Jacksonville, FL; Mayo Clinic, Rochester, MN; Memorial Healthcare Systems, Hollywood, FL
Background: A prior study of intra-CSF topotecan (TOPO) for unselected pts w/ NM reported PFS 6 mo of 19%, and OS of 15 wks (Groves, NeuroOncol 2008;10:208). We postulated that greater activity might occur in pts w/ malignancies considered sensitive to topoisomerase inhibitors. Methods: We reviewed outcome of women with NM and adenocarcinoma of the breast, ovary or lung receiving IVe TOPO (0.4 mg 2x/wk x 4wk, Q wk x 4, Q 2wk x 2, Q mo x 3, Q 2mo x 3, and Q 3mo x 4) until progression (PROG) or adverse events (AE). All had baseline CSF cytology, and MRI of brain and spine. CSF cytology was obtained at each treatment (Rx), and brain/spine MRI Q 3mo. Neuro-specific PROG was defined as recurrent 􏰂 CSF cytology; PROG of NM on MRI; all-cause neurologic worsening; pt refusal; or death. PFS/OS were measured from 1st TOPO Rx. All pts signed consent; the study was IRB approved. Results: 17 women (breast -12; lung-3; ovary - 2) were treated via Ommaya reservoirs; 7 (41%) had VP shunts w/ valves, adjusted for Rx. Median (med) age was 53 (41-79), and KPS 70 (50-90). At presentation, 11(65%) had 􏰂 CSF cytology and 14 (82%) had NM on MRI [brain-11 (65%); spine-10 (59%)]. 15 (88%) had no prior intrathecal Rx. 13 pts (76%) received focal RT for CNS disease, and 8 (47%), chemotherapy for extracranial disease. Med.number of Rx were 13/pt (range, 3-50); med. duration of TOPO Rx was 14 wks (range, 1-109). Med. neuro-specific PFS was 13 wks; PFS6 was 41%, and PFS12, 29 %. Med. OS was 33 wks (range, 5-180), w/ 4 alive at 13􏰂, 30􏰂, 33􏰂, and 180􏰂 wks. 4 pts (24%) lived 􏰁 95 wks. Of 11 w/ baseline 􏰂 CSF cytology, 7 (64%) cleared CSF of malignant cells (med. duration clear 􏰃 47 wk (range, 9-104). AE included arachnoiditis (18%), leukoencephalopathy (18%), and Ommaya infections (12%). Rx was stopped for neuro PROG (29%); systemic PROG (23%); refusal (18%); AE (12%); or persistent negative CSF (6%); 12% are still on Rx. Conclusions: Promising activity of IVe TOPO was observed in women with NM from breast, lung and ovarian cancer. PFS 6 and 12, OS and cytologic response were twice that noted in prior studies of NM pts w/ unselected malignancies. This data supports our plan for a phase II study targeting this select cohort.

[Lani]

another pertinent ABSTRACT:

2052 General Poster Session (Board #13G), Sat, 1:15 PM-5:15 PM
Concurrent intrathecal methotrexate and liposomal cytarabine for the treatment of leptomeningeal metastasis from solid tumors.
Brian J. Scott, Homira Feely, Tiffany Brown, Vincent Van Vugt, Ryan Kim, Paul Timothy Fanta, Lyudmila Bazhenova, Santosh Kesari; University of California, San Francisco, San Francisco, CA; University of California, San Diego, La Jolla, CA; University of California, San Diego Moores Cancer Center, La Jolla, CA
Background: Leptomeningeal metastasis (LM) from solid tumors is typically a late manifestation of disease with a median survival of weeks to a few months. Treatment is palliative, with no widely accepted standard of care. Options include intrathecal (IT) or systemic chemotherapy, radiation therapy or ventriculoperitoneal shunting. Randomized trials comparing single agent IT methotrexate to liposomal cytarabine have shown similar efficacy and tolerability. There is limited data, however, on the use of combination IT chemotherapy in solid tumor LM. Methods: We conducted a retrospective cohort study of 19 subjects treated for LM from solid tumors at a single institution. In addition to therapies directed at active solid tumor sites, each subject received IT liposomal cytarabine plus IT methotrexate injections every two weeks. Survival data and treatment-related toxicities were determined by systematic chart review. Results: LM was diagnosed by CSF cytology in 12/19 (63%), while the remainder were diagnosed by clinical and MRI findings. The most common cancer types were breast 7(37%), glioblastoma 6(32%) and lung 3(16%). The majority 18(95%) had active systemic or parenchymal brain disease at the time of treatment, requiring systemic chemotherapy 18(95%) or radiation therapy 13(68%). The median number of IT treatments was 4(range 1-9). Treatment was interrupted due to toxicity in 3(17%), while 7(37%) experienced 􏰆 CTCAE grade III toxicities, most commonly meningitis 3(16%). Treatment was stopped in 7/19(37%) following complete cytologic response 6/11(55%) or radiographic clearance 1/7(14%). The median overall survival was 96 days(n􏰃6; range 29-158), median time to neurologic progression was 46 days (n􏰃9; range 6-101) and the most common cause of death was progression of systemic disease 4(67%). Conclusions: Combination IT chemotherapy was reasonably well-tolerated, even in a population also receiving chemotherapy for progressive systemic disease. IT-related adverse events occurred at rates similar to previously reported single agent trials. Prospective evaluation is necessary to determine whether there is a survival benefit compared to single agent IT chemotherapy.

[Lani]

and another:
2070 General Poster Session (Board #16A), Sat, 1:15 PM-5:15 PM
Prospective follow-up of a cohort of 112 patients with leptomeningeal metastases of breast cancer recruited from 2007 to 2011: Prognostic factors.
Fahed Zairi, Nuria Kotecki, Isabelle Rodrigues, Marie-Christine Baranzelli, Charles Andre, François Dubois, Patrick Devos, Matthieu Faivre-Pierret, Richard Assaker, Jacques Bonneterre, Emilie Le Rhun; CHRU, Lille, France; Centre Oscar Lambret, Lille, France; Université Lille Nord de France, Lille, France; Centre Oscar Lambret - Université Lille Nord de France, Lille, France
Background: Around 5% of patients with breast cancers (BC) will develop leptomeningeal metastasis (LM). The incidence may increase. Methods: We reported the description and outcome of 112 consecutive BC patients diagnosed with LM in our institution from 2007 to 2011. Correlations between characteristics and overall survival (OS) were analyzed using usual statistical methods (Kaplan Meier, Log-rank, Cox model). Results: BC were invasive ductal carcinoma in 69.7%. Estrogen and progesterone receptors were detected in respectively 61.6 and 44.6%. HER2 expression was observed in 26%. 23% were triple negative. Median time between BC diagnosis and LM diagnosis was 44 months. At LM diagnosis, median age was 54 and median Performance Status (PS) was 2. CSF cytology and cerebrospinal MRI were positive in respectively 72,5% and 87%. 103 (92%) LM patients received IT liposomal cytarabine as 1st line of treatment (ventricular device in 47%). IT therapy could be associated with systemic treatment in 58% of the cases and cerebral radiotherapy for LM in 14% of the cases. Clinical response after 1st line treatment was observed in 57%, CSF response in 30,5%, MRI response in 62,5%. 24 patients received a 2nd line of IT thiotepa, 6 a 3rd line of IT methotrexate. The more significant prognostic factors (p􏰀0,0001) were initial PS, associated systemic treatment and triple negative BC status. Other significant predictors of OS were thiotepa as 2nd line treatment (p􏰃0,0004), intracranial hypertension at LM diagnosis (p􏰃0,019), associated cerebral radiotherapy (p􏰃0,02), progesterone receptor status (p􏰃0,04). Median OS of the 103 treated patients was 3,8 months (4,75 months for 0-2 PS and 1,6 months for 3-4 PS patients). Conclusions: Median OS was consistent those of other recent cohorts of BC LM. Our results confirm the role of a very early diagnosis, before the degradation of the general status. The association with systemic treatment or cerebral radiotherapy is indicated when possible.

[Rolepaul]

Alexandra1

Yes. Nina's was a left breast of 6.0 cm with 4 out 20 lymph nodes positive.

The 5% LMD is going to go up because of the Herceptin being able to get most everything other than brain and spine. If other areas than the cancer in the LMD was never noted, but it is estimated it would have been found in most of the patients (source not able to be cited for fear of being terminated.) We need to get positive results and get them now. The info from ASCO is great. I will start looking at this from a pharm guys viewpoint.

Paul

[Rolepaul]

To all, there is hope with brain mets. Nina's MRIs show only normal background in the brain and spine. The PET scan came back as normal. The tumor markers are down to the normal population. There are no abnormal cells seen in the Lumbar Puncture or a vein draw. Treatment is going to nce every two weeks for the Intrathecal (and we hope the IV). TDM-1 works, but only if there is not Central Nervous System involvement. This approach will be investigated for those individuals with brain and spine mets from Herceptin based disease. We cannot thank the doctors at MD Anderson enough.

[calisa71]

Just got dx with lepto. I want the intrathecal Herceptin trial. Anyone with any info to expedite getting into this trial PLEASE help. I am terrified. Anyone been through this I'd love to talk.


Thank you very much

Lisa. (calisa is just an onscreen name)

[marvass]

We are doing it and rolepaul is doing it too.
Chicago are recruiting now, 10mg twice a week.
France trial are recruiting now 30mg per week.
But maybe you can get a better trial through your oncologist if you convince him. If you need more details message me or rolepaul who is more of an expert. Good luck

[Rolepaul]

Lani,

So the clinical trial shows an overall survival of 3.8 months on average. That is unacceptable! Intrathecal Herceptin has been shown to eliminate the detectable presence of Leptomeningeal disease in almost every case that has been noted in literature or on the internet if at least 50 mg per week is used. I was contacted by one gentleman whose wife died, but of liver or pancreatic cancer a few months after treatment. Most of the other patients are still alive, or passed away from other causes years after the treatment. It took four solid days of work to get all the information about this treatment method for Nina and getting treatment started was extremely difficult due to politics of not having the number of cases out there to make the doctors comfortable initially.

Dr. Raizer is struggling to get women for treatment. That is what is even more frustrating. The studies at Northwestern and in France are not well advertised, without the completion of the trial there is no documentation of positive results, without positive results there is no knowledge in the community or health industry to inform doctors and patients. Dr. Razier's study is to determine the amount of Intrathecal Herceptin that is tolerable. There are already 12 patients that have 50 mg or more per week. I would have thought that it would have been higher dosages than the 10 mg twice weekly or 20 mg twice weekly lower dosages.

Nina is already down to once per two week treatment with NED in the brain, spine, or anywhere else, Mario's wife has already started treatment, Lisa looks like she should get her treatment started within ten days, and there are other contacts I am working with to get this done through compassionate care if they can't get into the Northwestern trial. If there are the numbers of patients with Lepto disease as it sounds like, there are too many for this trial. There is talk of MD Anderson personnel getting a large scale trial started, but the provider of Herceptin, Genentech, has some reservations about providing funding for a large study. They need to have some "push" to get this concept going. I am pushing NCI, NIH, ACS, Susan B Komen, and anybody else I can to get some help for a trial.

Let me know what we need to do from your thoughts.

Mario's wife Carol is now at 50 mg per weekly dose. MRIs in three weeks to show progress. I feel like I am a one man army, but getting recruits as people find out about how to fight this war on Lepto involvemenr with HER+.

[dchips1]

my 6 week thoracic mri after 20 rounds of rads, showed slight reduction to my lesions. hurry up and wait for 7 more weeks for next Mri. Still on Tykerb 750mg and weekly Herceptin, tumor markers are good. i have never had any CSF samples for cells? These 2 different lesions are pretty much inoperable.It is kinda crazy that her2 + can wiggle around inside the spinal cord so crazy.

Very interested in possible treatment using Intrathecal herceptin if the radiation doesn't kill it all the way to NED!!

Barrows neurosurgeon will place omaya, but not to sure about the Herceptin use? is it the same Herceptin vials that you get IV, but use different diluent?

Can you still wear an ATV Helmet with the omaya reservoir in place? My anniversay present

Prayers and Love To all Of our warriors and Cargivers

Darita
Arizona

[Rolepaul]

Ommaya does not need any other protection than you normally do. They put the Ommaya into the head and it is just like a vaccine when they give the treatment. It is the same Herceptin as used via IV. They use 5 mls of sterile saline or water for injection to dissolve the amount of material targeted. Please contact me via private message and I will give you the contact information at MD Anderson and they will take your doctor's call to let you know what was done for Nina. All I want to tell you is that this will take a compassionate care protocol at the hospital there. I will do everything I can to help you.

Paul

[Rolepaul]

By the way, yes you can still wear an ATV helmet. I did not read that carefully. You probably need to give it a few days to heal up from surgery, maybe cut just a bit of padding if there is any interference, but I think you should be okay.

Please contact Dr. Raizer at Northwestern on how he is formulating the Herceptin if you cannot get in touch with MD Anderson. See me a Private Message for contact information for me, MD Anderson, and Dr. Raizer.

[calisa71]

I am in touch with Shanu modi at msk. Sent her some info from md Anderson. If Shanu and Amal could speak that could help. I am a established pt with mskcc.
Lisa

Shanu Modis email is modis@ mskcc.org.
646-888-5243

[dchips1]

pertuzumub has the same molecular weight as herceptin, would be interesting if we could add or use this in altering treatments with herceptin intrathecal therapy?

Darita

[calisa71]

Darita. Is the cancer in your csf or just spine(bone)?

[dchips1]

Both of the lesions are inside the spinal canal and sitting on a nerve or two. In the thoracic area t3-4 and t-8. I have had 20 rounds of radiation to both the areas.

Darita

[evlin75]

My daughter is in the Chicago trial. Just had her first treatment. How long does it take to know if the medicine is working?
Thanks for any info.
Ev

[KDR]

Calisa71,
I am Dr. Modi's patient. Are you treated on Fridays? (I've been there so long, so often, surely I must have seen you). You can PM me.
Karen

[hutchibk]

If I am not misreading this (which I could be...), I believe that intrathecal Herceptin is available at every clinic as an approved treatment, as long as your Onc is doing it and insurance covers it.

[Rolepaul]

The is a likelihood that she will have nausea and vomiting with the first treatment. That would be the best indicator it is working as it means the cancer cells have been destroyed. First MRI from now will show it is working otherwise. What was the dose? Please post what happens.

[evlin75]

My daughter is receiving 10 mg two times a week for the first month in the Chicago trial. She is getting herceptin only IT- no other additive. She also gets Herceptin IV - along with Tykerb that she has been on prior.

[evlin75]

Finally very good news! Daughter was feeling better after two injections of the higher dose 60 mg, and had a couple really good days last week. Now we have found out the cytology results from last week's draw shows degenerating mastastases type cells in the sample. They draw samples each week during the treatment.

Now the doctor has scheduled 80 mg for the next treatment. He said the degenerating cells shows we are finally getting somewhere.

I am elated that he seems agreeable to upping the dose of herceptin IT to where it needs to go to get rid of the cancer cells.
She is still taking Tykerb but carefully as it does cause some stomach upset. she is also still getting the herceptin and Perjeta in the vein port.

She gets her new Ommaya next week so maybe even better perfusion and less painful sticks. Keep your fingers crossed that his Ommaya port installation and healing goes well this time. They will be installing it in the same well healed area as the one that became infected and abscessed.

This was a GOOD day! May everyone here have some good days too.

Ev

[Rolepaul]

I have tears in my eyes. I was so frustrated with the doctor. The goal is 1.5 mg/kg of body weight. Your daughter is truly exceptional, as are you. Never give up. Hate to lose.

[evlin75]

Thanks, Paul,

You have been a great help to many others - my daughter and myself- during this troubling time. 80 mg will be getting very close to the 1.5 mg per kg for my daugher, Susan, as she has lost so much weight and is now at about 120 lbs. I am feeling that we have won this doctor over finally and if we need to go higher he will do it for us.
I am breathing a big sigh of relief today as now she has a chance.

Ev

[Rolepaul]

They should see improvement in the MRI scans in the next eight weeks. I would hope she is clear of lesions by mid-May. Have them make sure to give steroids if there is dizziness or nausea when they bump the dose. I let some people meeting in NY tomorrow know about this. Patients need this option and doctors need to know about this type of result. You owe me a soda when we meet. I prefer Coke Zero, no ice.

[Rolepaul]

Keep up the good news. Evlin, Please PM with the doctor treating Susan as Monica Botero wants to see the center and get similar treatment.

[evlin75]

an extra note here- this physician may not take other patients. he is doing this cautiously in consult with other MD Anderson physicians.

[marvass]

So glad for you Evlin, I am so happy for you. Once you keep pushing you get what you wish for, and sure Susan will be cured! Wish you luck with the new ommaya.
Mario

[MonicaB]

I thank you all those who fight the good fight. As more patients are taken care of with good results, I don't understand why they are not taking other patients. I'm one of them in need of a chance

[evlin75]

Monica, I sent you a private message. I think compassionate coverage will become more available soon.
More physicians will be more comfortable about doing the Herceptin IT therapy.
Some day it will probably be approved for first line treatment for brain and spinal cord mets with the Her2 diagnoses.

Ev

[evlin75]

Well a hitch in the procedings and the ommaya surgery canceled for now. Her EKG showed some T wave abnormality. She has to make an appointment with her cardiologist and get cleared for surgery before they will do the reservoir.
I know anemia and central nervous disease can cause T wave changes. She is anemic because of the chemotherapy.
Anyone else run into this situation?
She is not having chest pain or any other symptoms. We just found this out today and the surgery was scheduled for Wednesday.
Thanks for any input.

Ev

[MonicaB]

:( T wave changes are not specific for ischemia. They probably want to be sure her cardiac function is within normal limits. You are right if Susan has anemia ans was tachycardia at the time, that could do it.

[evlin75]

thanks Monica,
Susan has a cardiologist so will have him review everything carefully to be on the safe side. I have not seen the EkG so have no idea what type of abnormality they are talking about. They found the problem during the pre-op series of testing Friday and then compared it to an earlier EKG from her oncologist's office.
We want to be safe above all. Maybe her cardiologist will be able to see a safe path through this so she can still get the reservoir put in.
In the meantime she goes on with the lumbar intrathecal treatments.
Always something!
Ev

[evlin75]

Update:
Susan did not receive 80 mg today but remains on 60 mg. The doctor said he did not want to change the dose prior to the surgery. This was the fourth dose on 60. The spinal fluid tested clear last week.
Next - the visit to the cardiologist. Hope his evaluation will allow rescheduling the surgery soon so to allow better perfusion of the medication.
Ev

[MonicaB]

Good news that she received it :) and that the spinal fluid is crear!! :):):). She is in my thoughts and prayers to get the Omaya and up on the dose. Than is for keeping us posted

[evlin75]

Susan had a few uncomfortable days after her last treatments - some vomiting.

She had the IV treatment of herceptin and perjeta and then the next day the intrathecal treatment of herceptin and toptecan. She needs to separate the treatments in the future and NOT do them back to back.

The cardiologist cleared her completely by EKG and ultrasound. Said she had a healthy heart. That is very good news all around as she can now have the ommaya replaced and it also indicates the Herceptin in the larger doses is not harming her heart.

Her doctor gave her the 80 mg today. That is the dose recommended according to the 1.5 mg per kg of body weight. She sees the neurosurgeon again tomorrow to begin again the process of setting up the ommaya surgery replacement. The cardiologist expressed shock that they canceled the former surgery scheduled since he found no problems.

I am relieved. Her next MRI is next Tuesday.

Ev

[MonicaB]

All good news! So happy for Susan and you:) well deserved:):):) with endurance, perseverance and help from friends like the ones joining this forum...my heroes! .brighter days will come :)
Thank you all!
Keep posting good news:)

[evlin75]

Another uplifting interesting case with a positive outcome.
Ev
http://www.oncologypractice.com//fileadmin/content_pdf/co/6_CO_july_232_Brandt_Case.pdf

[evlin75]

The Ommaya was replaced today using the opposite side this time. The procedure went very well according to the neurosurgeon. She was admitted for observation for two days - I guess the standard routine. She has a headache of course but normal neuro checks.

Now to keep it safe from infection until it heals well.
It is good that this part is over so she can get her treatment using the ommaya instead of the lumbar punctures.

Ev

[evlin75]

To Rolepaul:
What is the highest herceptin mg IT being given at the Houston MD Anderson? If our physician does not feel comfortable about going higher we would like another avenue if Susan needs it.

Ev

[evlin75]

I certainly wish much success to all who are doing the IT treatment for spine mets, but my daughter is having a very rough time right now.
She finally got up to 80 mg the last treatment before the new ommaya was placed, but the subsequent MRI showed progression all along the spine. Several spots in the cerebellum, a more prominent area in the thorax and more also in the lumbar region. He changed her treatment to a more toxic chemo Lysomomal Tycaribine (sp). He is concerned that it is getting out of control. He wanted to discontinue the herceptin as it cannot be mixed wth the new medication. I did not agree with stopping the Herceptin so she will get it on alternate weeks. Because this is a more toxic medication, she receives steroids before and after the treatment.
She gets the stitches out of her ommaya site Monday. Tuesday she will be admitted to the hospital for the flouroscopy and the areas in her spine that are grossly enlarged will be radiated. She will also receive her herceptin that day.
I am told she will have to stay overnight for observation. We were so hopeful for the Herceptin but maybe the lumbar punctures were not getting it all into the right area as some were very painful. It is good they can use the ommaya now though.

Ev

[dchips1]

Prayers headed your way Darita

[JennyB]

EV,
I hope the new regime starts to show improvement for your daughter, sending prayers from down under.
Jenny

[marvass]

Wish you luck with this new treatment.
Mario

[evlin75]

Guess I should change title or start a new thread, but this is all very connected. The new medicine replacing the topotecan -lysomal tykarabine- was put through the ommaya last Wed. She was prepped with medications -including decradon and then given steroids for two days following.
She did fine for a couple days and then started continual vomiting so is in the hospital trying to get it under control.
The vomiting is not new with her and has happened before the new medication was started. Has been hospitalized for it before.
She was due for radiology to check the spine for obstructions and get them radiated Tuesday, but now is in the hospital a couple days early. I guess more testing will be done to rule out other possible causes.

[dchips1]

how long does the pain of the Ommaya surgery take to subside? bending over is not a good thing, neither is drinking to fast, coughing, blowing nose or messing with ears. Tommorow will be 8 days. since placement. talk about pain. hope prayers and shout outs for good scans and healing to all Darita

[NEDenise]

Darita,
Prayers going up for some relief for you! I think of you often, as you blaze this trail. I hope IT Herceptin is exactly what you need to kill this beast once and for all!

Did the doc who placed the reservoir have any advice about pain management or its duration. I don't think any kind of pain is "normal" or okay...until I check it out with someone. Too often, we Mom-types just grit our teeth and muddle through...when we should have said something.

All the best to you! Keep us posted!
Denise

[evlin75]

Update on Susan.

She is receiving the depocyt every two weeks IT now x five doses. and then will go to once a month. So three more of the every two week before the once a month. It seems the slow release depocyt gives the most side effects on the third/fourth day.

When those kick in she has a very bad day or two. At first, even with steroid prep she was endlessly vomitng and she seemed to have the brain inflamation reaction. Had to be hospitalized. Now the doctor has ordered the steroids to be continued past the old schedule to 4mg once a day continually. However this time two days after treatment she had trouble with walking and fell. Also sleeping continually.

Dr. Monica Loghin MD did consent to talk with me about her case. She thought the local neuro-oncologist was doing all that could be done and going to Houston would not help. She is still getting the 80mg of Herceptin IT on oposite weeks from the depocyt. They cannot be mixed.

The Houston doctor said it was not a good sign that the leptomeningeal areas progressed while on Herceptin 60 mg as Herceptin usually keeps it stable even on lower doses.

She had talked with the Orlando Dr and seemed to think Susan's condition and areas were much more advanced that some others that have had success. For that I can try to blame her old oncologist for not picking up on the disease sooner. Susan had to ask for the MRI.

Dr. Loghin continued to say that Herceptin IT research is in such an early stage. She indicated some have success with only 20 mg and some with 40 mg. Susan did not have success with 4 of the 60 mg doses and one 80 mg dose. It could not even keep her stable. I believe, from her statements, Dr. seemed to think that the disease had overridden the herceptin and the topotecan.

So far she is still getting the IV perjeta and Herceptin through her port to help control any total body problems.

Hopefully the depocyt wil get the rapidly spreading cells in the spine under control, as the other treatment set up had stopped working.

Ev

[schoonder]

Treatment with T-DM1 frequently works after Herceptin fails to be efficacious. Could use of this compound be considered to help restore control over the cancer?

[evlin75]

Hard to know. We were wondering about using perjeta IT. It was very difficult to find a doctor willing to do the higher dose Herceptin.
Your suggestion of TDM1 -or even pergeta - IT, might be something to consider but again unapproved and experimental so what doctor would chance trying it?
And of course the guidelines for TDM1 are such that it would not be available to her at this point.

[schoonder]

Ev,
It's all so difficult, too difficult. Wonder if Genentech could be of any assistance, maybe make either drug available for compassionate use. Anything to help turn the tide.

[evlin75]

I have been traveling and doing appointments and home for a short time. Meanwhile other family members have been busy researching for answers.
It seems that methotrexate given parenterally through her vein port and the depocyt through her ommaya could possible bring good results. They seem a good combo for irradiating tumors in the spine. It claims methotrexate clears the spine better given intraveneously than intrathecally to remove the growths when given in combination with the depocyt.

So maybe we try that next. Will run it by the doctor.


This is the info on mtx


Numerous reports suggest that systemic therapy improves survival for patients with LM.72 (http://archneur.jamanetwork.com/article.aspx?articleid=799479#ref-nnr90015-72),93 (http://archneur.jamanetwork.com/article.aspx?articleid=799479#ref-nnr90015-93)- 100 (http://archneur.jamanetwork.com/article.aspx?articleid=799479#ref-nnr90015-93)Some authors feel systemic therapy is the most important part of the treatment of LM73 (http://archneur.jamanetwork.com/article.aspx?articleid=799479#ref-nnr90015-73)- 74 (http://archneur.jamanetwork.com/article.aspx?articleid=799479#ref-nnr90015-73)and exclude intrathecal therapy in patients with responsive cancers.94 (http://archneur.jamanetwork.com/article.aspx?articleid=799479#ref-nnr90015-94)- 95 (http://archneur.jamanetwork.com/article.aspx?articleid=799479#ref-nnr90015-94),97 (http://archneur.jamanetwork.com/article.aspx?articleid=799479#ref-nnr90015-97),101 (http://archneur.jamanetwork.com/article.aspx?articleid=799479#ref-nnr90015-101)Agents capable of producing adequate CSF concentrations following systemic administration may benefit patients with LM.


Methotrexate.Methotrexate inhibits dihydrofolate reductase and the synthesis of purine nucleotides and thymidylate, interfering with DNA synthesis and repair. At high doses, methotrexate has favorable CSF penetration. A prospective, nonrandomized study comparing intrathecal methotrexate (n = 15) vs high-dose systemic methotrexate (n = 16) in patients with LM produced provocative results. High-dose methotrexate (8 g/m2over 4 hours) resulted in a mean peak concentration of 17.1 μmol/L in the CSF; cytotoxic CSF methotrexate levels remained measurable much longer than with intrathecal dosing. Furthermore, there was higher CSF tumor cell clearance and survival was longer (13.8 months vs 2.3 months, P = .003) in the systemic methotrexate-treated cohort.102 (http://archneur.jamanetwork.com/article.aspx?articleid=799479#ref-nnr90015-102)Because of the favorable pharmacokinetics of high-dose methotrexate, further studies in patients with LM are warranted, possibly in combination with other agents.

[Jackie07]

Lani has posted a new abstract on the procedure: http://her2support.org/vbulletin/showthread.php?t=57507&highlight=methotrexate

[NEDenise]

Ev,
No new advice...just wanted you to know that I'm thinking of you and Susan...and praying for strength, continued love, and a quick reversal of all those symptoms!

Just for the record...I pray for a CURE everyday...and Susan's name is in the litany...believe me!

With love,
Denise

[alexandra1]

Im really flipping out. The doctors more or less yesterday said that my wife is about to die. They more or less said they are throwing the kitchen at the cancer. Her brain is building up fluid and were gonna hopefully have a solution for that today so that we can start intrathecal herceptin. along with that they want to give pretuzamed which is a large molecule. They think the brain barrier could be down because of the disease. They also said that the cancer is resilient to radiation and has now becoming resilient to chemo's The first thing we need to do is take care of the fluid backing up so that she can get intrathecal. The second question is im looking for a list of small molecule chemo's I can find one I always end up with the biologics. Im flipping my lid and cant imagine what life is without my wife and how my 3 little girls are gonna handle this.

[europa]

I am so sorry to read your post. I am going to pray for your wife and your three little girls. I am so sorry you and your family are going through this. I pray that they are able to drain the fluid and give her the IT Herceptin.

[marvass]

Peter, IT herceptin will work, but you need steroids to clear the fluid immediately. My wife was in a similar situation last year in April, but now she is nearly clear.
Hope you succeed. Praying for you
Mario

[schoonder]

One can only imagine that organizations like NCI or NIH would provide critical information such as contents provided in prior post to oncologists which are, by their own admission, at road's end. Before throwing in the towel, any KNOWN procedure, even ones that only have remotest chance of working, MUST be attempted. All man-made laws and legalities become pretty insignificant when facing death.