stopping temodar and other plans

Mark's most recent blood test showed some low nutrophil counts again, so the doctor has asked him to stop Temodar for a couple of days. We'll get another blood test on Monday to get the counts checked out again. Monday is actually our last day of radiation and they were planning on having us stop the chemo then anyway. We're planned to have a 2 week break of both drugs and treatments and will be having a MRI on March 15th followed by a consultation with UCLA on the same day. March 16th we're meeting with Dr. Liau to discuss Mark being able to participate in her dendritic cell vaccine trial. UCLA plans to have Mark start on a stronger dose (400mg) of Temodar for a 5 days on, 23 days off regimen. Depending on how things go with Dr. Liau, we're also thinking about making a visit to Duke and to UCSF, but haven't yet set the plans. If possible, we'd like to see if we can plan the trips during spring break so we can all travel together. Overall, Mark has been doing great! He really hasn't been too fatigued or nauseous. He's started training for his bike ride and has been holding up well!

Mark is training for the LIVESTRONG Bike Ride!

One more week of radiation to go! So far, he's doing great and we hope that he continues to stay healthy. Our new family struggle is not unique. More than 10 million Americans are currently living with cancer. More than 1.3 million people in the U.S. will be diagnosed with cancer this year alone.

In honor of Mark's battle with cancer, and for all of those millions of people in the same fight, he's participating in the LIVESTRONG Bike Ride in Irvine on June 25^th. He's planning on riding his bike 100 miles to raise money for the Lance Armstrong Foundation. His ultimate goal is $15,000. We just bought him a sweet new road bike and he's currently training every day for this event. He's going to do his best to stay strong for every mile.

The Lance Armstrong Foundation believes that in the battle with cancer, unity is strength, knowledge is power and attitude is everything. Founded in 1997 by cancer survivor and champion cyclist, Lance Armstrong, the LAF provides the practical information and tools people living with cancer need to live life on their own terms. Their mission is to inspire and empower people affected by cancer and they serve this mission through advocacy, public health and research programs.

We know he can reach his goal with the support of friends like you. If you're interested in helping him, you can give online at www.livestrongride.org

Next, click on: “Support a Rider”, click on Southern California and then type in “Mark” “Pace” .

Please ask your employer if they offer matching gifts, which could double your donation.

Thank you for your consideration :)

UCLA followup during radiation/chemo

We had a followup appointment with UCLA to discuss questions/concerns while mid-treatment.
Here's what we found out:

We met with Dr. Leia Nghiemphu and Dr. Cloughsey

Blood pressure 115/59 temp 97 weight 171lbs height 5’9” (178.5cm)
Neurological exam, all was fine.

How are you doing with radiation/chemo? Doing fine, but have some constipation, not feeling nauseous. Use Miralax, whole grain, lots of fluid, prune juice.
Blood tests being done every week? Yes. Dilantin has been in range, no seizures. Expected date that radiation stops is around 2/28, we’ll need to come back 2 weeks after radiation to get MRI (around 3/14). If you get them at UCLA, they can be read that day and are in the system; however, it is more convenient to get them at Hoag, but you have to make another appointment to have it read at UCLA.

We will probably be switching to Kepra – side fx can make you sleepy, usually get used to in about a week, can also make you irritable (but this is unpredictable on who it happens to), at beginning you are taking both temodar and kepra so you can be eased into it. You won’t need to get blood levels for Kepra. Will take 2 tablets twice a day is the goal. For first 3days, just take 1 2x a day (500mg each). Have a regimen that tapers us off dilantin

Has been complaining of vision problems (reading fine print). Radiation can dry out your eyes and may be affecting your vision. Wait until 2-4 weeks after radiation to assess. 43 is probably a good time to check your vision.
Has a little bit of spacial disorientation. Probably still having residual effects from surgery and anesthesia that could be causing this; also, radiation/chemo can effect this as well.

Can you look at our pre-radiation MRI and compare to operation report that said there was a thin irregular rim of enhancement? This is normal after surgery, could be there forever, may be scar tissues. We worry when things are thickened or have nodules.

Any time frame yet on when we'll hear results about the EGFRvIII and PTEN protein tests? These are done on research time, so there is no set date when this will be done. The results can help determine what drugs will be effective on a recurrent tumor. Molecular marker treatments that can identify the signaling pathways. Our reports show that this is probably being done now. They have been stained, Dr. Paul Mishel is doing this with data coming out of UCLA, he interprets these results and is also a researcher. Waiting for interpretation.

Some patients do well and tumor doesn’t come back for 2-5 years. Can come back within 6 months (quite rare and usually older patients) and would indicate that temodar not effective.

In the pathology report, it talked about 2-3 mitoses? What is the significance of the number? These are the dividing cells and there are a lot of them in GBMs.

Still a bit congested and wondering about chest results…can you explain what the SUV is on the PET scan we had a few months ago? It is clear and showed no activity.


Are there trials for upfront GBMs? Why did we not know of these trials? R115777 radiation/temodar study that had no openings at the time we needed to go through standard treatment. Verinostat (saha) is a current trial about to open on that is done in combination with temodar which is a phase 1 study, so we don’t know if it leads to strong drop in blood count or what the other side fx are that can be associated with it. Still trying to figure out what dose (phase 1). Having a meeting tomorrow to discuss this new trial. Being run at 9 different centers and each opening can only take qualified candidates. Gets evaluated every month. Would we be eliminated if we do dendritic cell therapy? Would have to do after dendritic cell therapy.

What about gamma knife leading edge? Can it be done after radiation? Don’t do gamma knife. It is like setting fire on your tumor, you have to do it very carefully or you can spread the fire to areas that spill over where you don’t want it. It can spill over into your speech center. Would be risky. Series of phase 2 data accumulated showed some positive results, but phase 3 (randomized) results showed that it didn’t make a difference

What about an MRI spec? Only needed when you have a tumor present and has to be at least 1cm in size. Kind of a messy test and gets a lot of false results. Can be mixed up with normal brain to get half a signal.

When will we be switching to Kepra? Can do it now.

How long will we stay on bactrim? Only through radiation and daily temodar. Once on monthly temodar, take bactrim only if counts drop too far.

Any precautions about getting a massage while still going through radiation/chemotherapy? Don’t do any brain massage ;)

What is considered a WBC level that we should be concerned about? We look at absolute nutrophil count to determine if chemo needs halted.

What are antineoplastons? Treatment being done in Texas by Burzynski, which involves a mixture of vitamins. We don’t know if it works or not. Have had 10 patients here that have done it, maybe it worked for 1;however, data really hasn’t been published about it, so its tough to know if it works. Not approved by FDA, have to pay cash for it. Have to go there to get IV.

What other trials are available to us (besides dendritic cell therapy) ? Right now, none. Most trials are mainly for recurrent tumors. Most upfront trials are during radiation, which we’re half way through now.

Are 3 year survivors all that you have? No we have more (he gave me names, but I don’t want to publish them on the website)

Duke likes to alternate chemo therapies. Different philosophy here. They switch it to avoid failure; however, we have no way of predicting which chemo will work for you. If chemo #1 worked, then you go on chemo #2 and it failed, it doesn’t really show which one is the one that caused failure? In theory it is good if you can know which chemo therapies are going to work for you and then you can alternate. It can decrease your options later on if the tumor comes back.

What is the difference between gene therapy and immunotherapy? Gene therapy changes your DNA (none currently available for brain cancer). Immunotherapy you try to boost immune system to attack your tumor (dendritic cell).

Have you heard about the TK gene? Thymodine. Kind of like a vaccine trial, but would need injected into your tumor, meaning another surgery. If tumor comes back and there are surgical options, this can be discussed.

Since we’re now having radiation, if the tumor came back, would a form of brachtherapy be relevant? No, it gives a lot of radiation to rim of tumor and that is near very eloquent areas and it could spill over. Would be risky in our situation and could effect speech.

Can I get more info about Sulfasalazine as a way to treat GBMs? Being used, but we haven’t seen good results yet. Lots of side fx with it. We use it later on if other things are not working. May be considered if tumor comes back. The treatment originated from studies at University of Alabama Birmingham. You can find more info if you internet search for H. Sontheimer. I read that UCLA does do this, it is part of your planned regimen?
Not really Can you give me more info about what it does/risks/side fx? Headache, stomach upset, diarrhea, rash, can rarely have some severe side effects. We have used it in several patients. We would only use it after we have tried a lot of the other options.

What does UCSF propose? Similar to how they do things here at UCLA. We have a lot of the same trials. UCLA, UCSF and Duke also have several trials together as well. Sometimes they have trials that we don’t but usually the same. May differ in what clinical trials are available, but not necessarily better, but can be something to try.

Questions about Liau’s trial?
Should make appointment when we know when radiation is over. (I just set this up)
She gives you three shots of vaccine then back on temodar, will need to talk to her about what the procedure is now. She now has another protocol where she administers the vaccine along with temodar.
Is it still needed if there is no known tumor still there? Always assume that the tumor is there, and it would be useful.
Does it go along with temodar? Usually she has you take a break, but she has been changing her protocol.
How long is it administered? Once a month shots for 3 times
Takes frozen tumor from surgery, grinds it up, looks for markers, develops antibodies then injects it back in.
Does the WBC have any effect on when he gets the vaccine? White cells are what makes the antibodies, she wants your immune system to be good in order to help these antibodies do their job. Similar vaccine trials being done at Cedars and UCSF (just started).
Dr. Liau’s treatment does well on fairly young upfront tumor patients (like Mark).
If we stay on temodar for 2 years and there is no recurrence, what then? Stop, then watch with MRIs.

Would you advise us of trials that are not UCLA-related, or do we have to search these out on our own? We share a lot of trials and we’ll tell you.

Can I surf? You probably can surf, but make sure you’re healed well and wait till after radiation.

We heard that a prolonged use of temodar has risk of the patient developing leukemia? Is this true? Yes, all chemo therapies have this risk. Temodar has the least risk, other chemos you can sometimes only stay on for 6months to a year, before the risk is higher. Temodar you can stay on for up to 2 years. Often if the agent did cause leukemia, it is generally not seen for 10 or so years. More risk of current tumor that possible leukemia.

I read that if the tumor comes back you cannot use temodar anymore? Is this true? We usually do not go back to more temodar in this situation. If so, what does your team propose to do next? Clinical trial or CCNU
There are numerous options that depend on each patients situation (repeat surgery, other agents (CCNU, carboplatin, Avastin/CPT-11, etoposide, clinical trials available at that time)

We’re concerned that we didn’t know about options for surgical treatments (i.e. gliadel wafers, live tumor tests, etc.) If we have to go to surgery again, are these things that you would make us aware of, or do we need to do the research ourselves? Gliadel wafers have been out since 97 and not that many people use them. Only 10% of academic centers use them. EDR has a problem as well…it has never been proven to predict what sensitivity the tumor has toward the different drugs, because the tumor for the tests is grown in different environment. Good in other tumors, but not necessarily GBM.

If we had to go into surgery right now, what would be the best method? Good resection is best for now along with trials and/or chemo.

If we mix up the drugs and the tumor comes back, can none of those drugs be retried? Right, it is hard to tell which is the drug that failed you.

We're concerned about the cause possibly being something in our environment.
Since we have a young child, we'd like to see if there is any link to our area.
If we were going to test our soil/water for possible contaminants that could possibly lead to cancer, do you know what chemicals we might test for? Don’t know any chemicals or toxins that cause GBM, so don’t know what to test for.

blood brain barrier – in your brain, you have blood vessels that go to the brain. There is a barrier where blood can’t just diffuse into the brain. there are special transport mechanisms. With GBMs, the blood brain barrier is already disrupted. Temodar is known to be able to get into the tumor

We had a pre-radiation MRI done at Hoag last week. Did you receive the
report from this? Do you have any comments about what you see in this MRI in comparison to the one we had post surgery? There is still blood within the cavity, there are changes around the cavity, but impossible to say what these represent. The latest MRI will be a good baseline to compare subsequent MRIs.

Do you have statistics about what percentage of people that GBM resections have to come back and do something again? This happens in the majority of situations
Is there an average amount of time that you see regrowth even after starting radiation/temodar? Are there some people that have regrowth even during standard therapy?

After we are done with our treatments, when will the bigger dose of temodar start?
Will there be a break between last day of readiation/chemo before getting on the 5days/month plan? This will start 2 weeks after last day of radiation Ok, so the last day of radiation is also the last day of the 150mg Temodar and then we stop for 2 weeks before starting the 400mg temodar? yes Will bactrim still be needed in this interim period? Depends on his white count

Dr. Christopher Duma

Last night Dr. Duma was a guest speaker at our brain tumor support group. He was a great speaker and had many interesting things to say....

Dr. Christopher Duma
Medical director of gamma knife program at Hoag
He does ~150 craniotomies a year and ~200 gamma knife procedures a year
There are a number of ways of improving outcome than what used to be available in the past
Biggest improvement is operating microscope, but since then, little has occurred until neurosurgical navigation (mri with real time intra operative guidance about 10 years ago)
Using navigation with microscope is the standard of care for any brain surgery that exists today. Navigation allows smaller cranial openings and smaller pathway to get through brain to tumor.
When you open a head, you usually can't see the tumor because they are usually deep. Used to use ultrasound to help find the mass, but sometimes that wasn't good enough. With computer navigation it makes it much easier, gives millimeter accuracy.
Improving outcomes
Gamma knife is good for metastatic tumors (tumor cells travel in the blood to the brain). Cyber knife also can be used for these types of tumors. Gamma knife has a more accurate focus and less radiation to the brain, but can only treat tumors within the brain. If out of reach of the gamma knife (spine, skull, etc.) cyber knife is used.
Implanting gliadel wafers (soaked with chemotherapy) into the cavity, if it is in the lobe of the brain (not deep) is also an option.
People are now starting to try gamma knife for GBM (newer technique). GBM tumors are able to migrate through the brain. Difference between I and II and IV is ability to migrate through the brain. Tests done on tumors to check migratory ability of astrocytomas, they found that the more aggressive ones become irregularly shaped and start looking and moving like an amoeba, they start spreading and getting polarized and start getting the ability to contract and move on their own (kind of like an inchworm)! When in-utero, brain forms as a ball of neurons in the middle of the skull, at a certain point of development, they migrate to proper positions to form brain. With GBMs, cells are reverting back to primordial way and regain the ability to migrate again. We want to fix it so they can't migrate. An experiment was done taking a GBM and put it in a jar...they radiated it with low dose radiation, then did high dose radiation (like gamma knife) found that cells moved more if they got low dose radiation vs 4x less if they received a high dose of radiation. Adding a high dose may help stop the migration, if they can't migrate, the cells will hopefully die off. At Hoag, we've been radiating leading pathways of GBMs to cut tumor off at the pass (callaed gamma knife leading edge); however, we still sometimes faile because tumor cells can migrate farther than we can imagine, you need scans that can show where the growth is (MRI spectroscopy that can show chemicals in areas in brain that can show where tumor growth may be).
Best chemotherapy adds 3-4 months survival (5% alive at 2 years). Our outcome (including gamma knife leading edge) has 20% survival at 2 years. My philosophy is to incorporate everything and throw it at the tumor. 1st start with good resection, radiation, boost, temodar during and after, gliadel on recurrence, more chemotherapy. (There are other approaches out there as well...i.e. Dr. Friedman (Duke) uses mostly temodar with other chemo agents)
Temodar is #1 drug for treating GBM. Original papers show it works well for grade 3, doctors started using it off label for GBM. Big study showed marked improvement for Temodar and GBMs (Stupp regimen). Studies show that it really has the ability of crossing blood barrier and being effective. New trial going on (Europe and USA) with 800+ people in study to look at effects of Temodar. If tumor recurs, then they are no longer valid for this trial and fall into the Hoag trial for gamma knife on recurrent tumors. All brain tumor patients should be getting scans every 2 months at minimum, at first sign of progression, you need to start doing something. We have had a patient on temodar for 4 years. There are risks of various cancers (leukemia) with all chemotherapies, but odds of succumbing to new cancers are low compared to the brain cancer itself.
Immunotherapy has improved outcome greater than temodar and gliadel wafer studies. Immunotherapy is currently in trial and only for upfront GBM. The idea is that our bodies will hopefully develop immunity to daily exposure. White blood cells have been educated and often know how to fight disease that they've already seen (i.e. chickenpox). We hope to make you immune to your own brain tumor by programming your white blood cells to fight brain tumor cells and destroy. Our trial takes some white blood cells out of your body and we "supercharge" them (make them angry toward the tumor) for about a week with a substance (interlupen 2?). Through another craniotomy, we pour mixture (or paint it) into the tumor cavity so that they can get in and fight the foreign matter (tumor cells) then go out into lymph cells and educate other white blood cells to fight any cell that looks like a tumor (bad guys). Hoag has a patient out 9 years with gamma knife to leading edge and immunotherapy.
Has a patient (8 years) resected, radiation/chemo, 6 months later tumor came back, did gamma knife and immunotherapy, still alive today. How is Hoag's trail different than UCLAs? Not much different at all. Dendritic cells are white blood cells that present antigens to T-cells grown from tumor, injected into your arm vs being "painted" in. Both treatments "supercharge" the white blood cells, same concept, different approach. Hoag doesn't harvest from actual brain tumor, but puts them back in tumor cavity directly. UCLA harvests from tumor itself then injects it back in the body.

PET/MRI for brain tumors like these is worthless, it will never show leading edge of tumor and won't show you where tumor is going. MRI spec and MRI (with flair sequence) are the best for showing where the tumor is going. MRI spec can differentiate necrotic tissue vs aggressive cells (maliginant tumor).

Virtualtrials.com by Musella (who is a brain tumor survivor that set up this site) is an excellent resource to keep up to date on what new trials are going on out there for brain tumors.

Mark is a candidate for immunotherapy and gamma knife leading edge. Mark's tumor is in a lucky spot in the brain. His symptoms are often described as: Gerstmann syndrome (calculation trouble, disorientation)

Don't normally see necrosis so soon after radiation.

Duma doesn't do spines, backs or necks. He only does brain tumors and Parkinson's disease treatment(stereotatic-type of treatment). He does surgery, he picks neuro oncologist, helps follow up on scans, etc. Here's his website: www.cduma.com