Primary (CNS) Lymphoma in immunocompromised organ transplant patient with multiply masses

CNS metastases
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.

http://journals.lww.com/jto/Fulltext/2009/11000/Efficacy_of_Erlotinib_for_Brain_and_Leptomeningeal .19.aspx#

leprechaun2 said:

PCNSL treated with radiation
Hub was treated for 25 days with WBRT for his 3rd cns tumor. It exhausted him and took 4 or 5 months to get back to himself completely. He lost his hair, which grew back. He lost his sense of taste which also came back. His short term memory was definitely damaged but we went to cognitive therapy and she helped with learning to use both devices and techniques to overcome his loss. He couldn't read the paper then. Now he works on books.

after the radiation, which I think they have lowered the level of for treatment, he was taking rituxamab and it took 8 months for a new tumor to grow. his treatment was from March through April of 09. New tumor was found in Jan of 10. He underwent more methotrexate and then a stem cell transplant and is still here.

He is immunocompetant so I am unable to speak to that aspect of dealing with this horrible mess. I also can't speak to the whole deterioration process, we have fought tooth and nail against each of the side effects although all are present to some degree or other. We do PT for the walking, he sees a doc for the urination difficulties, we have OT/speech therapy for the cognitive losses. But he is able to enjoy each day we have and spends time with family and friends and I am happy each night that we have had another day together.

Sorry that you are both in this boat. When you do research on line, limit it to the most recent years in your search, much has been done for this type of cancer. I will keep praying for each of you...

Avastin for radiation-induced necrosis
When brain tumors are treated with radiation therapy, there is always a risk of radiation-induced necrosis of healthy brain tissue. Insidious and potentially fatal, radiation necrosis of the brain may develop months or even years after irradiation.

This poorly understood side effect can occur even when the most stringent measures are taken to avoid exposing healthy tissue to harmful levels of radiation. In most cases, radiation necrosis of the brain occurs at random, without known genetic or other predisposing risk factors. The only treatment options typically available for radiation necrosis of the brain are surgery to remove dead tissue and use of the steroid dexamethasone to provide limited symptom control. But clinicians have not found a way to stop the progression of necrosis, despite having tested a range of therapies including anticoagulants, hyperbaric oxygen, and high-dose anti-inflammatory regimens.

However, recent studies at M. D. Anderson have shown that the monoclonal antibody bevacizumab (Avastin) may be able to stop radiation necrosis of the brain and allow some of the damage to be reversed. Victor A. Levin, M.D., a professor in the Department of Neuro-Oncology and the senior researcher on the studies, said the findings suggest that radiation necrosis of the brain can be successfully managed—and perhaps even prevented—with bevacizumab or similar drugs.

The need for such a breakthrough is as old as radiation therapy for cancers in the brain. “No matter what we do or how good we do it, we know a small percentage of patients who receive radiation therapy to the central nervous system will suffer late-occurring radiation necrosis,” Dr. Levin said. “We used to think it was the dose that was causing problems. Then we did a study and found that there was little to no relation to radiation dose or radiation volume—the necrosis occurred simply by chance. So it is impossible to say which patients will develop this problem; we just have to monitor them and hope for the best.”

Like necrosis, the discovery that bevacizumab has an effect on necrosis can also be attributed to chance. Bevacizumab, a newer drug that prevents blood vessel growth in tumors by blocking vascular endothelial growth factor (VEGF), was originally approved in the United States for the treatment of metastatic colon cancer and non–small cell lung cancer. An M. D. Anderson group that included Dr. Levin decided to test the drug in patients who had VEGF-expressing brain tumors. “Some of these patients also had necrosis from prior radiation therapy, and we were struck by the positive response of those patients to bevacizumab,” Dr. Levin said. “We had never seen such a regression of necrotic lesions with any other drug like we did in those patients.” The observation prompted the researchers to design a placebo-controlled, double-blind, phase II trial sponsored by the U.S. Cancer Therapy Evaluation Program in which bevacizumab would be tested specifically for the treatment of radiation necrosis of the brain.

The trial is small, having accrued 13 of a planned 16 patients, and is limited to those with progressive symptoms, lower-grade primary brain tumors, and head and neck cancers. But the results have been unlike anything the researchers have seen before in radiation necrosis therapy. All of the patients receiving bevacizumab responded almost immediately to treatment, with regression of necrotic lesions evident on magnetic resonance images, while none of the patients receiving the placebo showed a response. The results were striking, and all of the patients who switched from placebo showed a response to bevacizumab as well. So far, responses have persisted over 6 months even after the end of bevacizumab treatment.

Side effects seen in the trial so far included venous thromboembolism in one patient, small vessel thrombosis in two patients, and a large venous sinus thrombosis in one patient. Dr. Levin is unsure whether the side effects were caused by therapy or the radiation necrosis itself. “We’re also not absolutely sure what is causing the positive effects against the radiation necrosis,” he said. “We presume it’s related to the release of cytokines like VEGF, since bevacizumab is very specific and only reduces VEGF levels. We think aberrant production of VEGF is involved with radiation necrosis of the brain, and the fact that even short treatment with bevacizumab seems to turn off the cycle of radiation damage further confirms the central role of VEGF in the process.”

The multidisciplinary research team has also postulated that radiation therapy damages astrocytes, a cell type involved in various brain functions, and causes them to leak VEGF. This leaked VEGF might then cause further damage to brain cells and further leakage of VEGF. “It gets to be a very vicious cycle,” Dr. Levin said. “The question is, is that all that’s going on?”

Dr. Levin hopes that the answers to that question and others may lead to preventive measures against radiation necrosis, beyond what is already done to control the development of radiation itself. Perhaps bevacizumab can be given in low doses before radiation or intermittently afterward to reduce VEGF levels and protect the brain from abnormally high levels of the protein. He hopes such approaches can be tested in future studies. “Just the fact that bevacizumab works has helped us understand so much more about what happens in radiation necrosis,” he said. “Everything we’ve tried up until now has been a brick wall.”

Source: OncoLog, May 2009, Vol. 54, No. 5

Visualizing the effects of Avastin (bevacizumab)

http://www2.mdanderson.org/depts/oncolog/articles/09/5-may/pop.html

Bevacizumab (Avastin) Reverses Cerebral Radiation Necrosis

http://jco.ascopubs.org/content/26/34/5649.full.pdf

prabuelita said:

Multiple masses in different locations of the brain PCNSL
Thank yo Leprechaun2. My significant other has seven or more tumors; three in the right parietal lobe, one in the frontal lobe, one in the cellebrum and two or more on the left lobe.

We will start radiation on Oct 7th. five days a week for 5 weeks. My significant other is immunocomprimised. Don't know if I spelled that right.

Thanks

Seems to be same tx hub had.
Seems to be same tx hub had. He was really tired as the weeks progressed. Provigil helped his concentration and focus. He started it about a month after the radiation was finished. His sleep immediatly cut down from 20 hrs/day to 10. I cannot say enough about how this helpedboth of us. Good luck to you both.