Anyone have mets to brain lining or spinal fluid? Muscle enzyme issues?

Leptomeningeal Carcinomatous
Cancer of the lining of the brain from breast cancer is called Leptomeningeal Carcinomatous (LC). Metastasis can occur through one of three processes: direct seeding of body cavities or surfaces, lymphatic spread, and hematogenuous (blood) spread. I've personally experienced my wife's case of direct seeding of an unevaluated spinal metastasis, which seeped through the meninges into the central nervous system (CNS).

In order to fully evaluate a leptomeningeal metastasis, cerebrospinal fluid (CSF) is obtained from a lumbar puncture (spinal tap). At first sight, the fluid would be cloudy (a sign of infection). A cytology test is performed 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 carincomatous. Each specimen is split for chemical, hematological, microbiologic, and cytological examination.

You cannot see this disease. It is happening more frequently, particularly when breast cancer patients are treated with taxane combinations. In my wife's case, microscopic circulating cancer cells seeded into the CNS, either by a violated blood-brain barrier or spreading through the bloodstream. She had a 3.5cm brain met one year after taxane combination treatment. However, she had a 1cm lesion on her spine left unevaluated by the radiation oncologist during radiation treatments. A year later, that lesion became three lesions, one of which seeped through the meninges into the CNS.

Patients with this disease present with signs and symptoms from injury to the 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 CSF flow pathways, or general interference with brain function. This is why my wife eventually fell and broke her hip in four places.

After looking at her clinical records, laboratory results, pathology reports and interviews, they obtained and examined cerebrospinal fluid in hematology, chemistry and microbiology, which showed adenocarcinoma nodules in her CNS. Evaluations of cerebrospinal fluid cell count reveals the presence of malignant cells in remarkable numbers.

The condition is very difficult to treat. The main aim is to help control symptoms and not cure the disease. Chemotherapy (generally Methotrexate) injected into the spinal fluid (via Ommya Reservoir in the brain) or radiotherapy to the brain are both treatments for LC. 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.

However, there may be more effective treatment for LC. A small molecule drug 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 EGFR pathway drugs, Tarceva (erlotnib) and Iressa (gefitinib), given together. It might cross the blood-brain barrier and some patients may get a long-lived remission with these drugs.

High-dose tamoxifen could then be given continuously as a potentiator and an anti-angiogenic effect. This suggestion comes from cell function analysis, by clinical oncologists involved with cell culture assay testing.

There has been clinical trials with molecularly-targeted Iressa for Leptomeningeal Carcinomatous from NSCLC. And some clinical trials using Temodar (temozolomide) instead of Methotrexate, Ara-C, or combination Gemzar (gemcitabine) plus Thiotepa in treating patients with LC from a solid tumor.

Iressa and Tarceva are very similar drugs, small molecule inhibitors of tyrosine kinase, a key intermediary in the EGF cascade pathway. They act on multiple receptors in the cancerous cells.

EGF is epidermal growth factor. EGF is a receptor on many normal tissues/cells, and also on many cancer cells. It is a growth hormone, locally secreted by cells. It attaches to a receptor on the cell membrane called EGFR (epidermal growth factor receptor).

It then activates signalling pathways withing the cell (a cascade of biochemical events). One type of enzyme which is involved in the pathway is called tyrosine kinase.

Targeted treatments like Iressa and Tarceva take advantage of the biologic differences between cancer cells and healthy cells by "targeting" faulty genes or proteins that contribute to the growth and development of cancer.

So, in different tumors, either Iressa or Tarceva might get inside the cells, better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.

I'm sure that Tarceva or Iressa would be more tolerable than Methotrexate, a mean and nasty drug. And you don't have to take Tarceva intrathecally.