OH what to do???
 

Hi all well things had been going well until ??? Last week had slight vision problems shaky vomiting. I had MRI done on brain and got really good new two of my tumors shrunk fro 6mm and 7mm to 2mm. Great now the bad news the big rotten one has grown again from 17mm to 23mm and i have a new problem mengines (not sure how to spell this but basically cancer) which is the layer of tissue between brain and skull in the frontal lobe. This has caused me my vision problems. Not sure of m next plan of attack i could have gamma knife on my grown tumor. But the lining of the brain not to sure. It must be smallish as they are not sure if the thickening is this. But side effects would indicate that it is.

I also have a sore back only when i walk not while sleeping and sometimes lying on the floor helps. If any one has any ideas? I think Brenda my have had some cancer in brain lining.

Thanks all I really wish my roller coaster ride would give me a break soon.

Lot of love to all
Jacqui xx

Re: OH what to do???
 

Does anyone know of pertsutinab cross into blood brain yet?

Re: OH what to do???
 

No, pertuzumab is a very large molecule, like herceptin and does not cross the blood-brain barrier normally.

If you have leptomeningeal metastasis, intrathecal herceptin has been tried (Courtney had it, I believe, among others). Boswellia serata has been tried for l-m mets as well. Try using the search function above for leptomeningeal metastasis I know I have posted several articles about treatments in the past

Good luck!

Re: OH what to do???
 

Re: OH what to do???
 

Jacqui -
Really very sorry to hear you are having these problems. After all you have tried so hard to deal with the brain mets.

I pray that your team will have a successful treatment for you - and very soon!

Re: OH what to do???
 

I know nothing about brain mets, but I want to say I am sorry to read your news. Stay strong !!!!! Keeping my fingers crossed and hoping for success with what ever you decide to do.

Re: OH what to do???
 

Kiwigirl,

Sorry to hear about the new development. Below are two abstracts related to the subject (I believe both have been posted by Lani before) You might want to e-mail the writers directly (Curie Institute is supposed to be conducting a Phase I-II clinical trial. And the writer mentions Tyrosine-kinase inhibitor at the end of the article. http://en.wikipedia.org/wiki/Tyrosine-kinase_inhibitor )


Breast Cancer Res Treat. 2011 Jun;127(3):841-4. Epub 2011 Mar 3.
Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab.
Oliveira M, Braga S, Passos-Coelho JL, Fonseca R, Oliveira J.
Source
Medical Oncology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023 Lisbon, Portugal. mafalda.moliveira@gmail.com
Abstract
Trastuzumab, a monoclonal antibody against the HER2 receptor, is a major breakthrough in the treatment of HER2+ breast cancer. However, its high molecular weight precludes it from crossing the intact blood-brain barrier, making the central nervous system a sanctuary to HER2+ breast cancer metastases. We prospectively assessed functional outcome and toxicity of administering trastuzumab directly into the cerebrospinal fluid of a patient with leptomeningeal carcinomatosis (LC) and brain metastases from HER2+ breast cancer that had already been treated with other intrathecal chemotherapy, with no benefit. Upon signed informed consent, weekly lumbar puncture with administration of trastuzumab 25 mg was begun to a 44 year-old women with metastatic breast cancer (lymph node, bone, lung, and liver involvement) previously treated with tamoxifen, letrozole, anthracyclines, taxanes, capecitabine, intravenous trastuzumab, and lapatinib. She received 67 weekly administrations of intrathecal trastuzumab with marked clinical improvement and no adverse events. She survived 27 months after LC diagnosis. A complete leptomeningeal response, with no evidence of leptomeningeal metastasis at necropsy, was achieved. We believe that intrathecal trastuzumab administration should be prospectively evaluated to confirm clinical activity and optimize dose, schedule, and duration of treatment.


Bull Cancer. 2011 Apr;98(4):417-24.
[Leptomeningeal meningitis related to breast cancer overexpressing HER2: is there a place for a more specific treatment?].
[Article in French]
Gutierrez M, Lyazidi S, Brasseur L, Cvitkovic F, Le Scodan R.
Source
Institut Curie, hôpital René-Huguenin, 35, rue Dailly, 92210 Saint-Cloud, France. gutierrez@crh1.org
Abstract
Leptomeningeal metastases are very commonly associated with breast cancer. The prognosis is very poor in the short term with an overall median survival less than 6 months. Based on pragmatic and historical considerations intrathecal chemotherapy (IT) are considered to be the adequate treatment. However overall results are disappointing. Despite specific and symptomatic treatment, improvement in survival and quality of life remains very modest, highlighting the importance for ongoing research for developing new molecules or on improving the use a better use of those available today. The incidence of leptomeningeal metastases is particularly marked in cases of overexpression of HER2. The main hypothesis is there may be a better control of extra-cerebral localisations with trastuzumab therefore intra-cerebral recurrences may be encountered preferentially as they are not reached by this high molecular weight monoclonal antibody (148  kD). Analyses performed in the cerebrospinal fluid following intravenous trastuzumab showed extremely low levels of the antibody and support the hypothesis that leptomeningeal metastasis of HER2-overexpressing breast carcinoma remain potentially sensitive to HER2-type receptor inhibition by a target agent under the condition of by-passing the meningeal blood brain barrier. Intra-ventricular or IT administered with trastuzumab would reach high loco-regional therapeutic concentrations in the cerebro-meningeal without risk for normal non-expressing HER2 leptomeningeal tissue. This strategy has been successfully tested on several animal models. A limited number of administrations in humans have been described in the literature, with weekly doses up to 100  mg. No specific toxicity has been described and some data suggest a potential benefit in survival despite the real difficulties for adequate interpretations. Furthermore, a multicentric phase I-II clinical trial, of which the Curie institute is the sponsor and investigating the intra-thecal administration and the efficacy of the trastuzumab will begin very soon. More studies are needed to measure the exact impact of small molecule inhibitors of tyrosine kinase on the leptomeningeal localizations.

Re: OH what to do???
 

I'm sorry you had this news, my friend found lying on the floor reduced the pain from her spine mets too, just wanted to wish you well and sorry I have no advice.

Re: OH what to do???
 

Jacqui,

I'm so sorry for this rotten development. Cancer sucks.

I pray your doctors get this figured out soon.

Re: OH what to do???
 

Jacqui, I too am sorry for your news. I do not have mets but do have back pain it helps me to lay on a hard floor on my belly and spread my legs as far apart as i can. Odd Yes but it works. Gods blessings to you and your family.

Your Friend,

Nancy

Re: OH what to do???
 

Kiwigirl;

Sorry you are on the rotten BC mets rolllercoaster. I think I'm sitting right behind you. Searching this site for Loni's posts; I found this very helpful. I often refer to the BC mets site: http://www.brainmetsbc.org/
Hang in there. Keep fighting.
Love & Hugs, Kris....

Re: OH what to do???
 

A link with brain mets info:
http://her2support.org/vbulletin/showthread.php?t=42084

Re: OH what to do???
 

Hi all thank you all for your response it is a great help.I need to be strong but am really having trouble. So what they want to do is 10 rounds of radiation to Lepto sight in back of head and after my mri on my back do some radiation on my back. I'm really really not happy with this as it makes me so sick. Then they are talking about intrathecal herceptin also. Any way they are wanting to start on tuesday. I suggested gamma but once again the menages has to much swelling so no flying. I'm very nervous about this whole treatment plan. I'll up date once i find out more.

Re: OH what to do???
 

I'm really sorry you are dealing with this. All I can say is I hope your treatment is easy on you and you get to NED with it. Good luck and big hugs.

Re: OH what to do???
 

My wife had the same problem. The intrathecal Herceptin is scary, but should work. 80 mg once per week for a 60 kg woman was necessary for results. Add 2X wk topotecan. Get IV herceptin and navelbine (or T-DM1) as well. This worked within four weeks to clear brain and spine MRI scans. Reply with personal message if you want more info.

Re: OH what to do???
 

Gods blessings to you Jacqui. I will be praying for you and your family.

Leptomeningeal Disease
 

Kiwigirl

Unfortunately, cancer cells are too small to find on any scans unless they have grown into a lump. There can still be cancer cells in the body even though scans may have indicated that all the cancer had gone.

Cancer cells in the meninges is called by a number of names: Carcinomatous Meningitis (Lepteomeningeal Carcinomatous or Leptomeningeal metastasis), and is a condition caused by cancer cells getting into the thin sheets of body tissue that surround and protect the brain and spine. These sheets are called the meninges. Meningitis means inflammation of the meninges. Carcinomatous just means acting like a cancer. Most people are familiar with the type of meningitis caused by an infection, but with carcinomatous meningitis, it is the cancer cells in the meninges that cause the inflammation, not an outside infection.

Cancer cells do not always develop into an active secondary tumor when they have spread to a new site. Sometimes they stay inactive for many years. Even after a cancer appears to have been successfully treated, some cancer cells may still be elsewhere in the body. No one knows why some cancer cells stay inactive or what triggers them to form a secondary cancer.

Tumor cells reach the meninges by hematogenous (blood) spread or by direct extension from pre-existing lesions and are then disseminated throughout the neuroaxis by the flow of the cerebrospinal fluid. Patients present with signs and symptoms from injury to nerves that traverse the subarachnoid space, direct tumor invasion into the brain or spinal cord, alterations in blood supply to the nervous system, obstruction of normal cerebrospinal fluid (CSF) flow pathways or general interference with brain function.

Secondary cancers from a primary cancer can develop in different parts of the body, including the brain or spine. Cancer cells do not always develop into an active secondary tumor when they have spread to a new site. Sometimes they stay inactive for many years. So, even after a cancer appears to have been successfully treated, some cancer cells may still be elsewhere in the body. No one knows why some cancer cells stay inactive or what triggers them to form a secondary cancer.

Diagnosis is most commonly made by lumbar puncture, to look for malignant cells or elevated protein levels in the spinal fluid, although the CSF cytology is persistently negative in about 10% of patients with leptomeningeal carcinomatosis. A MRI of the brain and spine to look for enhancement of meningeal tissue. Radiology studies may reveal subarachnoid masses, diffuse contrast enhancement of the meninges or hydrocephalus without a mass lesion.

Doctors estimate that about 5 out of every 100 patients who have cancer develop carcinomatous meningitis. It is most common in breast cancer, but it can occur with any type of cancer. The cancer cells in the meninges can cause a range of symptoms, including confusion, headaches and weakness, also head pain, cranial nerve involvement, hearing problems and back pain.

The condition is very difficult to treat. The main aim is to help control symptoms and not cure the disease. Chemotherapy injected into the spinal fluid (via Ommya Reservoir in the brain) or radiotherapy to the brain are both treatments for Carcinomatous Meningitis. Some patients respond to these treatments, but the prognosis is generally poor. There are no set guidelines for treating this condition as oncologists don't really know which treatments work best.

Traditional treatment has been radiation therapy to symptomatic sites and intrathecal Methotrexate. The FDA has just recently approved a drug for Methotrexate toxicity. Voraxaze (glucarpidase) is an intravenously delivered recombinant enzyme.

Another alternative to Methotrexate is Cytarabine (cytosine arabinoside) or Ara-C. It is an anti-metabolite (like Methotrexate) which stops cells making and repairing DNA. Cancer cells need to make and repair DNA in order to grow and multiply. Ara-C is a clear liquid that can be dripped into a vein (intravenous infusion), into the spinal fluid (intrathecally) or by an injection just under the skin (subcutaneously).

There have been some clinical trials using Temodar (temozolomide) instead of Methotrexate, Ara-C, or combination gemcitabine (Gemzar) plus Thiotepa in treating patients with CM from a solid tumor.

There may be more effective treatment for this disease. A small molecule drug (a tyrosine kinase inhibitor that Jackie mentions), like Tarceva may be able to penetrate the blood-brain barrier (BBB). Small molecule intervention can be beneficial by dissolving through the capillary cell membranes and absorbed into the brain.

What may be another alternative is high doses of two small molecule TKI's (Iressa and Tarceva), given together. High-dose Tamoxifen could then be given continuously as a potentiator and an anti-angiogenic effect. There have been clinical trials with Iressa for this disease in NSCLC. I'm sure that Tarceva and/or Iressa would be more tolerable than Methotrexate, a mean and nasty drug. And you don't have to take them intrathecally.

Best of luck!

Greg

Carcinomatous Meningitis: Taxane Induced?

http://cancerfocus.org/forum/showthread.php?t=648

Re: OH what to do???
 

Jacqui,
Sheesh! I'm sorry to hear you're having so much trouble. I'll be praying for relief from the nasty side effects, and a quick return to NED.
Hugs
Denise

Re: OH what to do???
 

Kiwigal, Just sending along my very best wishes for a positive outcome. Ceesun

Re: OH what to do???
 

thank you all for your support it seems to quite a tricky thing to get rid of. So far I'm having radiation which my onc said he could get a great result and get rid of this. I only have three rads left and to be honest i not sure i believe him. The symptoms come and go i have blurred vision in morning sometimes a sore back (spine) and feeling sick and lost wanting to eat and blocked ears. And of course this makes you feel down. Thank you Rolepaul as your info from you was very helpful. My is the leptomenigeal mastitis in the menages. I'll keep you posted as to what we do next.

Luv to all
Jacqui