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[payton49]

My Freind has just been told that her Myeloma has spread to her brain. The doctors are going to treat her with chemo via a lumber puncture. Can anyone tell me what to expect.

Thank you

[gdpawel]

Intrathecal refers to injecting chemotherapy directly through the meninges, avoiding the blood brain barrier (BBB), into the cerebrospinal fluid (CSF).

An ommaya reservoir, a plastic, dome-shaped device, with a catheter (thin tubing) is implanted in the brain to facilitate the uniform delivery of the intrathecal chemotherapy into the central nervous system (CNS).

Placement of the ommaya reservoir requires a minor surgical procedure by a neurosurgeon, with the patient placed under general anesthesia. The reservoir is placed just under the scalp with the catheter positioned into the cavity of the brain where the CSF is formed.

This enables multiple rounds of chemotherapy in a single access site, so as to increase the comfort and reduce stress and pain associated with repeated injections in a site like the spinal column. They can also use the reservoir to sample CSF for cytology.

The only agents licensed for intrathecal chemotherapy are Methotrexate, Cytarabine (Ara-C) and Hydrocortisone.

With the ommaya reservoir attached inside the brain, frequent spinal CSF analyses can take place. Diagnostic evaluation of the fluid is looked at for chemical, hematological, microbiologic and cytological examination. Chemical analysis includes protein and glucose measurements, which typically would show an abnormally high number of mononuclear cells with elevated protein and low glucose levels (you cannot see this disease).

Ever since my wife's second CSF tap (when Methotrexate was already being administered), all of her taps were negative for ten consective times. A Whole Body Bone Scan indicated that the skeletal system demonstrated normal uptake and an enhanced brain MRI showed no new areas of abnormal enhancement. Leptomeningeal Carcinomatous (Carcinomatous Meningitis) has a very poor prognosis, however, the cancer cells were eradicted completely from her central nervous system.

Although we used Methotrexate back then, from what I know now about Temador, we definitely would use it instead. And if whole brain radiation (WBR) would be indicated, we would value the Temador chemotherapy instead of going the route of WBR.

[gdpawel]

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.

There has been clinical trials with molecularly-targeted Iressa for Leptomeningeal Carcinomatous from NSCLC.

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.