June 18, 2009
Charlotte started her Temodar tonight. Her Avastin is still being held because her UPC is still greater than 2.0. The UCLA study trial will only allow someone to be off Avastin for 90 days before they are dropped from the study. June 30th will be 90 days for Charlotte. I think Charlotte has clinically improved since being off Avastin, and her nephrologist is concerned about the long term effects that Avastin is having on her kidneys, so going off Avastin at this time is not so traumatic for us. Charlotte also had an MRI on June 13th. I have questions concerning some of the images, but I don't have the written report yet. The written report could change my mind about dropping Avastin.

Charlotte, Donna and I went to the Del Mar Fair today for 4 hours. Charlotte was, in Donna's words, just "awesome". She participated in an aerobics demonstration, had her picture taken with some show dogs, watched while Donna ate a cinnamon roll, and sat with me at the flower show. Charlotte did more in 4 hours at the Fair than she has done in the past year and a half!

Charlotte's energy medicine is named "Donna". There has always been a very special relationship between them for the past 40 years, and I have really observed it's effects every Thursday since Charlotte's journey began a year and a half ago. Every Thursday begins with the "normal Donna and Charlie", but by day's end, they both have enough vitality and exuberance to make it through the following week.
They are true soulmates!

May 21, 2009
Charlotte will begin her Temodar tonight. She came down with a "flu-like" viral infection on Monday, May 11th. She had a low grade temp, nausea, and most concerning, a low grade headache that was constant for seven days that even Tylenol would not relieve. The only food that she could handle was Ensure. On the sixth day, her fever finally went away, and she was able to eat some solid food. Her headache went away a few days later.

She obviously missed her chemo last week, so she is restarting her Temodar today. Her labs yesterday showed a UPC (urine protein creatinine) ratio of 2.1, and they will not restart Avastin until it is below 2.0. Her MRI came back stable and another test was not definative on telling us whether Charlotte's residual tumor
(what we actually see on the MRI) is actually tumor or radiation necrosis. I was hoping for that information, so without it, she will probably be restarting Avastin when the trial study allows it. Charlotte and I have some deep concerns about restarting Avastin.

The echocardiogram results showed some enlargement of Charlotte's heart. Just like the proteinuria, the Avastin increased her BP to the point that it was damaging both her kidneys and heart. We do have her BP under control for now, but only due to some very powerful BP meds that have their own side effects.
Right now, it is a toss up whether I'm more worried about the tumor, or the side effects of the chemo, radiation, and all of her other meds.

Brain cancer link.
I have Charlotte enrolled in the Virtual Trials case history and treatment section.
It's a good basic site to begin your journey.

April 30, 2009
Charlotte did not have her Avastin today. Sorry for my confusing update last time. When she does resume the Avastin, it will be at the lower dosage of 5 mg/kg. The Avastin will be held until Charlotte's urine protein creatinine ratio is less than 2.

Her urine protein creatinine ratio did fall from 8 to 6.8. At least we are heading in the right direction. I'm still getting some very high BP readings, but I'm also getting some normal readings too. Charlotte had an EKG yesterday and the cardiologist said the abnormalities were probably due to her high BP. She will have an echocardiogram tomorrow.

She will also have her MRI next week. I have noticed some clinical changes in her, so the MRI is coming at a good time. Hopefully these changes are not from the tumor, and being off of Avastin, but are from her radiation treatments, BP and proteinuria problems, etc.
I have received a lot off feedback concerning my links to other GBM information.

The first one is about MRI imaging analysis of GBM patients which contained nice images. Too technical for most, but was one of the best links that I have found.
This second link is just a touching story.

April 16, 2009
Charlotte will have her Temodar tonight, but we were notified yesterday that Avastin will be held due to the level of protein in her urine. I don't know if we will be able to continue with the UCLA Avastin and Temodar study trial. I did officially ask them to lower the Avastin dosage to 5 mg/kg from 10 mg/kg. The UCLA regulatory board is evaluating my request, but I am not optimistic for their approval.

Charlotte did see a nephrologist last week. Even with changes in her BP meds, her urine protein creatinine ratio jumped from 1.7 to almost 8.0 in the past two weeks. Her renal and BP problems have made her very tired. There are other other side effects that I am not happy seeing. We saw Charlotte's neuro-oncologist, Dr. Spier, last Monday. She was great about saying "O.K." to all of my requests.

While writing this update, I just learned that UCLA did approve the 5 mg dosage of Avastin. The following are two emails I just wrote, instead of rewriting this update:-

Hello Dr. Spier,
I just sent this to Nancy.
Even though we would not lose you if we went off study, sometimes doctors are not thanked often enough by their patients. I appreciate your help during the teleconference with UCLA.
Thank you for everything!

Hi Nancy,
What a surprise about the 5 mg dose of Avastin!
I had a massive headache yesterday, plus a feeling that things were starting to slip in a direction that I did not want. I have had a love/hate relationship with Avastin for the past three months, but that really was not my fear yesterday. My biggest fear was that if we did go off study, we would lose you.
I don't think you know how much we are truly grateful for you, and the work you do for us.
Thank you,
Brent and Charlotte

April 2, 2009
Charlotte had her Avastin today. Her lab tests yesterday showed her UPC (urine protein creatinine) ratio had risen to 2.9, up from 1.7 two weeks ago. The study trial will hold the Avastin treatments when the ratio reaches 3.5, so today was probably her last Avastin for a while. I have asked to see a cardiologist and a nephrologist ASAP. I hope these specialists will have more knowledge about Avastin, and the effects it has on BP and proteinuria. Charlotte's BP is out of control, and this was an avoidable situation.

I want to thank Nancy Grossmann (R.N.) at Zion Kaiser, and her study trial staff, for all of their conscientious and professional help.

March 19, 2009
Charlotte had her 14th cycle of Avastin and Temodar today. Her UPC (urine protein creatinine) ratio has risen from about 1.1 to 1.7 in the last two weeks due to the Avastin. Her last MRI results came back "stable" again.
We had a wonderful visit with her brother Gary and his wife Lorie last weekend. The picture below shows all of us on the sofa in the gallery.
Last week my update included information on Avastin. This week it is mainly about Temodar. Again, these are random lines from random posts from random people taken during the past two weeks. I thought these would be of interest to those of you that are fighting this terrible disease. (Thank you to all the authors.)
--------------------------------------------------------------------------------------------------------------------
Something else to worry about: "Temozolomide, a standard treatment for brain cancer, may boost the aggressiveness of surviving cancer cells, making tumor recurrence more likely, a new study suggests." This study is from Memorial Sloan-Kettering Cancer Center.
Re: Temodar promotes bad stem cells? Here's the link to the full paper

"Clinically, what we see with patients with glioblastoma is that after surgery, radiation and chemotherapy with temozolomide, they live longer and a subset of them will actually live a year, two years or even longer. And then pretty much 100 percent of the patients relapse and no one knows why."
"When you treat mice with temozolomide they develop recurrent diseases even quicker, so temozolomide make the cells that survive act in a more aggressive manner." "Temozolomide actually increased the number of drug-resistant cells. Because temozolomide doesn't target ABCG2, it may render surviving cells more resistant to treatments that do target the ABCG2 protein."

A paper presented at the last ASCO conference (google: asco 2008 Quant) concluded that once Avastin has failed that there is little benefit in trying other agents in combination with Avastin...

I also don't know if cediranib has been tried after Avastin but, personally, I think that's a reasonable idea, since it's an anti-angiogenic with a somewhat different mechanism than Avastin. I think that combining cediranib with lomustine (CCNU) also makes sense, since CCNU is a cytotoxic agent, although the toxicity always needs to be considered. "A safe bet: cediranib will be most effective with CCNU."

It's been a busy month for news already! In tomorrow's issue of the JCO (Journal of Clinical Oncology), an update on a study I've been following for 3 years will appear with very encouraging results. The regimen is essentially standard GBM therapy with an added dose of CCNU (lomustine) once a month. The results compared to standard therapy are remarkable. The new update in tomorrow's JCO. Moreover, I think this regimen could be a top choice for any newly diagnosed grade IV patient who does not get into a Novocure or vaccine trial, especially those outside the U.S. with a methylated MGMT promoter gene.

As another TMZ option for recurrent GBM, go to p863 at link to download Strik et al's full paper. One recent study that produced data re diffuse recurrence was Naranya et al.

Conclusions: Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored.

This may be a rather simplistic explanation but here goes: my husband has no progression around the original tumor area. Instead he has what has been termed a delicate invasive spread of the tumor cells in a quite large area- they barely even show on the MRI. These cells do not depend on making blood vessels the way that the GBMs usually do. Instead these cells live off of pre-existing blood vessels. They have taken different pathways that the Avastin is not blocking as they have mutated or learned to escape the stronghold that Avastin used to starve them. I don't think the Avastin "drives" the invasiveness. It's just what happens as the tumor cells find their way around the Avastin.

There are a number of angiogenesis compounds that can be secreted by cells when under distress due to shortage of oxygen and nutrients. Avastin targets only one of them: VEGF-A. My understanding is that if the cell is not 'satisfied' with the results of emitting VEGF-A, then nature has programmed the cell to begin to release other angiogenesis agents (I think there may be as many as 10 that have been identified). These other 'second-line' signaling agents may be giving the tumor a different growth pattern.

I agree that Avastin is very scary, but when faced with inoperable tumors, and if failure on TMZ happens, other than vaccine trials what options are out there?

"A new 600-page book entitled "Integrative Oncology" just came out, and I highly recommend it:"

March 5, 2009
Charlotte had her Avastin today. On Tuesday, her teeth were cleaned by her friend Grace Hansen. The picture below shows the two of them before the cleaning.

I would like to thank our friend Leena Hannonen for updating our website. She is presenting a series of mosaic workshops in Julian. Please visit her website. You can see all of the information at artelitedesigns.com

Charlotte's labs continue to show the effects of the Avastin on her body. There has been mention of Avastin (bevacizumab) on some of the brain tumor sites with some linked studies. Below are just random lines from random posts from random people during the past week. This is obviously not my usual update, but I thought this change was important. (Thank you to all the authors.)
................................................................................................................................................
We tried several other options but avastin was the only thing that was successful - even if only for 6 months. It gave him a chance to spend quality time with our children and grandchildren and to celebrate one more
Christmas.

So my bottom line is that I hope patients still consider using Avastin, but keep the emerging pitfalls in mind, and explore dosing schedules, combination therapies, and potential prophylactic treatments which maximize
the benefits while limiting the side-effects.

He likes to remind patients that "everything works in mice, but you are a human".

He is hugely full of hope, and truly believes we face chronic diseases, not terminal ones, and treats accordingly.

I don't think the article should be viewed as a universal condemnation of such therapies or Avastin in particular.

Patients should recognize both the known strengths and weaknesses of Avastin at the time of decision-making and avoid blanket statements which limit their options.

One of the general principles of cancer biology is that if one growth path is blocked, the cancer will try to find another path. In the specific situation of Avastin failing, we're in uncharted territory. However, given cancer biology, I would suggest going after 2 or more other growth factors, using something like Tarceva or a new multi kinase inhibitor. This is just a guess, however, in an area we clearly need suggestions!

This kind of aggressive treatment strategy may best be obtained from Duke, in keeping with what I understand is their reputation. You now need to move beyond using NIH as consultant.

The tumor is like a diffuse cloud.

Diffuse tumors tend to co-opt existing vessels rather than spawn new ones. That could be how the tumor is surviving - Avastin won't kill off normal existing vessels. Has anyone on these lists been able to effectively control their tumor once it has escaped the Avastin stronghold? If so how long has it been and what
have you used?

My son is in the same spot--he has failed Avastin. The tumor is spreading diffusely around, affecting his sight and speech. He is in a bad spot.

This news release in Science Daily addresses "angiogenesis inhibitors— succeeds at first, but then promotes more invasive cancer growth". Nothing new, for those of us who have been tracking the bevacizumab
story.

Has anyone on these lists been able to effectively control their tumor once it has escaped the Avastin stronghold? If so how long has it been and what have you used?
High vascularization of glioblastoma typically predicts poor prognosis.
Neovascularization (vasculogenesis and angiogenesis) is essential for tumor growth and invasion.
Vascular endothelial growth factor (VEGF) is a critical proangiogenic factor in almost all solid tumors. However, its expression and role in human carcinoid development and progression remain unclear.

The sometimes controversial cancer drug Avastin can cause kidney damage by doing what it's supposed to — but in the wrong place, a study shows. Edema is generally associated with tumor progression. Avastin has a half-life of about 20 days, and CPT-11 is less than a day, so if it's been longer than 20 days, your husband is officially off treatment.

These data indicate that stem cell-like tumor cells can be a crucial source of key angiogenic factors in cancers and that targeting pro-angiogenic factors from stem cell-like tumor populations may be critical for patient therapy. My understanding is that the cancer stem cell hypothesis is still under investigation and debate.

How bad is that? Well his tumor suddenly looks like a diffuse ghost spreading up through the frontal lobe and also crossing over a little into the other side of his brain. It's amazing that his scans were absolutely clean last time and now it's sort of everywhere. If it helps, Barbara, mine is in, and crossed the corpus, and is slightly into the right side, all that area is diffuse (not the lump seen elsewhere)

Are they absolutely sure that it is tumor? I assume that the changes that they are seeing on the MRI are on the T2 FLAIR images. But T2 FLAIR enhancement can also be from radiation/treatment related effect too. It can sometimes be very difficult to distinguish between the two on MRI images alone. If they are seeing mass effect, then tumor is likely.

He has been on avastin/temodar treatment and suddenly developed extensive FLAIR enhancement surrounding the right frontal tumor cavity, crossing the corpus callosum to the other side. It was very scary looking on the scan. The differential diagnosis at that time was radiation related change versus infiltrating tumor. He had no
symptoms. There was also no mass effect on the MRI. We went for a Dopamine PET scan at UCLA which was cold, so it was decided that the changes were not tumor after all.

The use of various contrast agents in MR imaging is becoming a challenging field of neuroradiology research. Iron oxide nanoparticles shorten T1 and T2 relaxation times, so they can be used in MR imaging of malignant brain tumors...

You have been quite an inspiration to all of us. May God be with you and my prayers are there for your fast and successful recovery.

Just because it is back again, does not mean it's going to win!!! The GBM has already tried to get me in 2000, 2004, and 2007 and never got the best of me! Now in 2009 I am going to beat the battle again. I'm ready for the
challenge.

Yes, blood glucose levels do make a big difference, both in prevention and treatment of most cancers (if not all). This is why so many researchers are interested in ketogenic diets, the IDH1/IDH2 genes, and other aspects of glucose metabolism.

I am so sad to read this - yet another challenge for you all to face. Diffuse tumors are so hard to measure. Maybe this can explain some of the clinical symptoms he has been having.

Also, here's a paper on aerobic glycolysis...

How to get the wacky stem cells under control!

O.K., I exhausted everything you have up that I hadn't already read.

Here's a decent article in Newsweek which I just stumbled across. It overviews cancer research, and largely echoes the findings of a previous article in Fortune by Clifton Leaf. www.newsweek.com

Here's a mini-lesson in chemo drug metabolizing. You can generally look up the metabolism of any drug by Googling the drug's scientific name and the words "metabolism" or "pharmacokinetics."
....All of these potentially cause drug interactions through interference with a key metabolizing enzyme called CYP3A4, part of the main family of metabolizing enzymes called cytochrome P450 (abbreviated "CYP").
.....Temozolomide (TMZ) is a prodrug, meaning that it is inactive by itself and only takes on its therapeutic qualities when it is metabolized. TMZ is hydrolyzed at physiologic pH to the active compound, MTIC,
without the aid of metabolizing enzymes. TMZ is essentially 100% bioavailable.

You might create some sample (food) menus of what a high grade brain tumor (patient) might take.

If metronomic TMZ has failed at 50 mg/m2, I'd be reluctant to try it at 75 mg/m2 because you would add toxicity and might not add to efficacy, though I could certainly be wrong.

Unlike P53 or PTEN mutations, IDH mutations only cause glioma but not any other cancers. Why it is so specific is with no doubt under intense investigation in academics. For us as patients, I care about how to make use of the findings in my treatment.... My first thought was IF (a big if) the loss-of-function mutation causes accumulation of isocitrate and a deficiency of alpha-ketoglutarate, and IF (another big if) alpha-ketoglutarate-deficiency indeed drives tumor progression, supplementing glioma patients with alpha-ketoglutarate may do the trick. This sounds like a crazy idea. It can not be this simple, can it?

Fatigue and balance issues are common in GBM for many reasons ranging from chemo to radiation to seizure medications to tumor progression. It's very difficult to pinpoint the cause.

I'm glad we have an international group here!

Malignant gliomas are highly lethal cancers that depend on angiogenesis for malignant progression

The base of pneumocytis pneumonia is a yeast, in the candida family. Steroids and antibiotic and temodar all can aide and abet this fungus. Candida in many forms is a HUGE issue for cancer patients, especially with meds and treatments and steroids.

I also recommend checking out the lively panel discussion on molecular oncology which can be found here.

Ultimately, your doctor is not responsible for your treatment and health. You are. Nobody is going to care more, or have a bigger vested interest in your survival, than you. And sometimes that means you have to think outside the box, and seek out evidence-based treatments on your own.

Thank God you guys are dedicated toward fighting this monster!

The following article explains the Avastin kidney damage (proteinuria) issue.

I just got my last MRI at UCSF last Friday. At that time I was told "It all looks good -the same and clear, no seen tumor". I drove home happy. Today I got a phone call from my Neuro-oncologist at UCSF.....

With Peace, Love and Hope...
God Bless...
Tons of love to you...
Wishing you strength....

February 19, 2009
Charlotte had her Avastin and will start her Temodar tonight. Lab tests show that her white blood cell count remains low, and Avastin is still making her kidneys produce protein in her urine. Another side effect of the Avastin is to cause her to have hypertension. Her blood pressure seems to have stabilized over the past few weeks, so we have not had to immediately go back on a third B.P. medication. Her sodium and chloride are still a tad below normal since she was discharged from the hospital.

We have had some inclement weather during the past two weeks, so instead of going for walks, she has been going up and down our back stairs. It is definitely more of an aerobic exercise than walking, and works a different set of muscles in her legs. It works her heart a lot more than just walking, which I like.

For the past couple of weeks, she just seems more tired than usual. Plus I think she has lost another four pounds, which does not make me happy. But I know her drugs are cytotoxic, and are influencing the tone of her muscles.

There are a lot of the doctors and nurses out with the flu, so I am trying to protect Charlotte from getting sick. She was out with me this past weekend trying to get fallen trees cut up. Over my objections, she told me that we have always worked together as a team, and this was no different. I finally convinced her to throw the ball for the dogs, in between supervising me.

February 5, 2009
Charlotte had her Avastin today and then we had our usual "get together" lunch with Donna and friends.
Charlotte's lab yesterday showed that her blood sodium level was still slightly low and her potassium level slightly high. These electrolyte levels are about the same since she was released from the hospital about ten days ago. Her neuro-oncologist pointed out that giving Charlotte "salt tablets", which she has been given in the past, could be dangerous. Raising the sodium level too fast in a brain patient could do more harm than good. I filed that away somewhere in my head because Charlotte has different doctors that prescribe medications for her different conditions. Comments and statements either get a little red flag (meaning I do not totally agree) next to them in my head, or a check mark (meaning it could be good upon further research). A little red flag went up about two weeks before Charlotte was admitted to the hospital on Jan 18th, and I blame myself for not looking into matters further.

The attending physician in the ER did make a comment about Charlotte's nausea and vomiting during her chemotherapy, and her statement received a little check mark. After confirming her statement, I decided to give it a try. Charlotte started her twelfth Temodar and Avastin cycle on January 22nd. It was the first time in a year that she did not have any chemo related nausea and vomiting. That allowed us to walk, work, etc., during this normally bad time of the month. We will see if next month produces the same results.

Looking back over the past year, there were two major things that made me feel so helpless. One was the sound of her vomiting during chemotherapy. That is why the above paragragh is such good news for us. The other was when I had to inject her with Neupogen to stimulate her bone marrow. The shots were given for three consecutive days, and she had to have them twice during the past year. The big side effect of the shots was to make her bones very achy. Waking up in the middle of the night hearing your wife moan and cry just to turn over in bed is something I will never forget.

On a happier note, Charlotte has expressed interest in writing a book about her brain tumor journey. She feels she has a lot to offer to her fellow comrades, especially with breast and brain cancer. I do not know the logistics of doing something like this, but I do think it would be a truly remarkable book.
I vividly remember going out and buying Dr. Susan Love's "Breast Cancer Book" with Charlotte right after her breast cancer diagnosis in 2001. We took turns reading it aloud to each other while trying to determine the best course of action.
Today, the type of cancer is obviously different, but the techniques remain the same for me. Learn as much about this disease as possible. Unfortunately, there is not one definitive book like Dr. Love's that we can go buy on brain cancer. Thank goodness for all the scientific sites like PubMed on the internet. There are a lot of things that I have learned that I wish I would have known a year ago, and those would be my contribution to Charlotte's book. Treatments are always changing, but one must know where to go to at least begin. I did not even know this in the beginning. I would like to pass this knowledge on to others.

I truly believe that with a glioblastome multiforme brain tumor, you only get one window of time to control this type of cancer. Obviously my job, along with others, is to learn how to keep that window open.

January 22, 2009
Charlotte started her Avastin and Temodar today.
Charlotte had a low grade nausea for most of last week and was accompanied by some vomiting as the week progressed. Charlotte's blood pressure also increased dramatically Friday night, and then her brain temporarily misfired. She had a somewhat similar condition right after brain surgery while staying in the hospital in December 2007. I asked her my name, her date of birth, and the names of our dogs. She could not say them, but unlike a year ago, she knew that she was unable to speak the correct words. She kept saying, "What is wrong with me, why won't the words come out?" She became very frightened. This "word to mouth" pathway has become noticeably more difficult for her. Realizing this, and knowing that I thought she did know all the names but just could not say them, I gave her a pen and paper on which to write. She proceeded to write the correct answers to all of my questions. I told her not to worry, it is just a matter of some physical therapy to retrain certain pathways in her brain. I do not know what caused this incident, but the positive is that she kept communicating to me that she knew what was happening to her. A wonderful book given to me by Mary is "My Stroke Of Insight" by Dr Jill Bolte Taylor: A Brain Scientist's Personal Journey. Charlotte's episode could have been an addendum to her book.

Then on Sunday morning she awoke with a headache, which meant an immediate trip to the emergency room at Kaiser. She was diagnosed with having a very low sodium level due to her vomiting and to a diuretic that she had recently been prescribed for both her BP and her kidneys. She was also diagnosed with a bladder infection. Charlotte was hospitalized after our ER visit, and on Monday she had a brain MRI to rule out any tumor growth or edema. Her MRI came back stable, so she was discharged late Monday, which helped us keep her next appointment at 8:30am on Tuesday with her neuro-oncologist. We also had an appointment today after the Avastin with her primary care physician to evaluate her blood pressure and her proteinuria, but was cancelled by his office early this morning. It will be rescheduled when he returns to his office.

Yesterday, after going to the lab for more tests and then off to pick up a copy of her latest MRI, she was able to put the finishing touches on a sculpture, dance with me in the kitchen to a Billy Joel song, and hug and kiss me about eighteen times.

What a beautiful and inspirational woman!
I am the luckiest man in the world....and I know it.

January 8, 2009
Charlotte had her Avastin today. Yesterday's lab work showed she had an increased level of protein in her urine. That is the third weekly lab that showed an increase. Right now we are just watching the level and hoping it does not get worse. Proteinuria describes a condition in which urine contains an abnormal amount of protien. Avastin can cause proteinuria, which can progress into kidney failure. Proteinuria has been associated with cardiovascular disease. High blood pressure can also cause proteinuria. Avastin also contributes to her high blood pressure.

It seems like it is a vicious circle, trying to control the tumor while still keeping the rest of her body healthy.
I remember reading some articles written by professional caregivers. The gist was more patients eventually succumbed to the side effects of their treatments than from their cancer. I do not know if that is true, but I still try to remember that everyday. It is so easy to live from one "stable" MRI to the next, and to forget about the rest of the body.

We are back walking twice a day, which is so important to her overall health. The rainy weather had reduced the number of walks for a period of time. I think her stamina is as good as it has ever been during the past year. Most importantly, she looks and feels great. Her ability to find the correct word when she speaks remains her biggest problem.

The wonderful pleaure she has is to wish her sister Donna a very, very
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!Happy Birthday!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

December 26, 2008
Charlotte's MRI on Dec. 15th came back "stable". She started her Avastin and Temodar today.
This has been one of the hardest months for her after her last Avastin and Temodar. She started with more nausea and vomiting, and her "chemo fog" has been with her for most of the time. Problems with her short term memory and her ability to find the correct words when speaking, seemed to have all slightly increased. All of this does not worry me at this time. We actually start laughing at her new language. She usually knows her wording is incorrect before I realize it. We will see how she does this coming month. I have read about patients receiving "stable" MRIs but also have clinical deterioration while on Avastin. That is something that would concern me, but her overall appearance and actions are still very good. Plus she can still play her flute and read out loud perfectly. Her artwork is getting more exquisite!

Last week I received a copy of all of Charlotte's MRIs on a disk. There were a total of ten MRIs dating back to November 26, 2007. I am trying to compare all of the MRIs to each other, and then compare each MRI to each written report. I have found a few good sites on the internet concerning how to interpret MRIs of GBM patients. My first big learning experience has come from comparing each of Charlotte's MRIs. I do not know the meaning of what appears on the MRI, but I can say that her brain has not been static during the past year. I asked a doctor if some of these "white wispy clouds" (axial T-2 FLAIR) meant more tumor, ischemic problems, brain softening, edema, or effects of treatments. This is something that I will try and learn myself, or through my long list of contacts.

I would like to thank Dr. Lai and Dr. Cloughesy at UCLA, and Dr. Polikoff, Dr. Spier, Dr. Silbert and Dr. Nordling at Kaiser in San Diego. I especially want to thank my brain researcher friends "Hong" and John Williams for helping me interpret some of Charlotte's tests. John, your wealth of knowledge is truly over-whelming, and your kindness in sharing is enormously appreciated. Your understanding and awareness of seemingly every GBM scientific abstract, both in vivo and in vitro, and the time that you must spend doing this research and then answering your emails from people like me, is just astonishing!
Finally, thank you Nancy Grossmann(RN) and your staff at Kaiser.

December 11, 2008
Charlotte had her Avastin this afternoon. The past two weeks have been very busy and sometimes confusing for us. First, we had Charlotte's teeth cleaned by our very dear friend, Grace Hanson. She reminds me so much of Charlotte. She is very competent, intelligent, and has that certain beauty both inside and out.
Charlotte's Avastin and Temodar just seemed to be a lot harder on her this month.
That has also been reflected in some of her blood counts. Some months seem overly good, such that I can not really trust them, and then some months they drop to a new low. Her blood pressure was extremely high again this morning. That has always been a constant battle.

Our philosophy, from both our personal experience and the experiences of others, is that you just have to take one day at a time. And as a caregiver, you must be aware conditions can change very fast. I am still haunted by the line from a friend's email that stated "I wish I would have done more for him". That is something that I never want to feel. Charlotte is on a cancer diet that may or may not be effective, and that is also why I had her teeth cleaned. Sadly these were never discussed in the beginning. But eating right, and trying to stop secondary infections from entering her body through her gums just seems to be the correct decision for us.
I still spend hours reading as many scientific abstracts that my mind can "comprehend" each day and night. Actually, when I first started one year ago, it was like reading a foreign language. I spent more time looking up and then writing down the definitions of these words. About two months ago, I sort of had an epiphany. I realized things were sort of making sense to me for the first time.

Emphasize "sort of"! I now have a new respect for all medical professionals and researchers, and all of their training. They are also in a field that brings forth new knowledge everyday. I personally can not understand how one individual can be fully informed in each of their specialties.

I want to mention that Charlotte had heart palpitations and vomiting last Sunday at 3AM. She had an EKG on Wednesday, but we have not received the results. Charlotte's next MRI is scheduled for Monday, December 15th. Those following five days are becoming more and more stressful for me. It usually takes about a week to get the results if the tumor is stable. But our neuro-oncologist will personally call us during those days if new growth should appear. I know the facts, and know our chances of avoiding that phone call lessen with time.
Charlotte's next Avastin and Temador will start December 26th.

We want to wish everyone a Merry Christmas, and a "thank you" for your love and prayers during the past year. Everyone has been so kind and generous that I do not know where to begin. I will not even try, except to say that I know that each and everyone of you have helped Charlotte fight her battle. And for that, I am truly humble.
Merry Christmas. Be well everyone. Love, Charlotte and Brent

November 30th, 2008
Charlotte had her Avastin on Friday, and we started her Temodar that night. She was suffering from a bad headache that was brought on by the Avastin for all of Friday. She told me late Friday that she felt that it would probably be best if we did not go up to Julian. For her to say that seemed very unusual to me. As I mentioned in the last update, it was one year ago at the Julian Christmas Tree lighting ceremony that she read some poetry. That is when we knew something was wrong. On Saturday morning she felt better, and decided that she wanted everyone to see and hear her reading poetry again.

She did a beautiful and inspiring reading of three poems on Saturday night! Unfortunately we had to return to San Diego early Sunday due to the side effects of the Temodar. We want to thank the wonderful Julian Library for inviting her to participate again.

Also, a very special "thank you" to Leena Hannonen of ArtElite (www.artelitedesigns.com) for designing our website and for posting our updates over the past year. Her expertise and friendship has made this past year endlessly more helpful and comforting for Charlotte and me. Thank you Leena for your many hours of work that you have generously given to us.
From Leena: It's been my plasure to be able to do this for you and I treasure your friendship.

November 18, 2008
Charlotte had her Avastin last Thursday, and will have her next Avastin and Temodar on Friday, November 28th, the day after Thanksgiving. Hopefully she will be able to attend the Julian Christmas Tree lighting ceremony the day afterwards, on Saturday November 29th. It will mark her "one year anniversary". It was at last year's tree lighting that she also read some poetry, and she started to have slurred speech. The next day she was diagnosed at Kaiser as having a brain tumor.

The attached five photos are a record of our progress over the past year. Obviously the first photo was taken before her diagnoses. The following photos show her at different times as she progressed during the year, ending with a photo that was taken just a few weeks ago. It's been quite a journey. One cancer researcher that comes to the gallery told me that many cancer patients have to reach their nadir before they seemingly get better. I would like to look at the pictures with that in mind. But, then days like yesterday happen. Charlotte woke up with a severe headache and was vomiting. That was very unusual. Always thinking of the worst first, I thought of possible bleeding in the brain from the Avastin. After watching her closely, and talking with her during the day, it turned out to be just another bump in the road that we've come to live with in the past year.
I've been busy trying to learn as much as possible about Glioblastoma Multiforme. Currently, I've been reading Charlotte's MRI reports from the past year and trying to educate myself on the terminology in the reports. Her latest MRI show that she has "chronic ischemic (inadequate supply of blood) small vessel disease" and a "contrast enhancing mass associated with postoperative encephalomalacia (softening of brain tissue by vascular changes). Then there is the residual tumor with "slight rim enhancement".



Every night I read more scientific abstracts on numerous GBM topics. It is over whelming, and sometimes quite discouraging, but I've always believed that knowledge is power. There is a whole world of information out there, from cancer diet to cancer therapies, that caregivers must research and learn.
One example is Ben Williams (teaches at UCSD) who was diagnosed with glioblastoma in 1995. The following is from his website.

“Treatment for GBMs and other high-grade gliomas is changing rapidly. Until the last five years there was a standard treatment in the USA , including surgery, radiation, and chemotherapy with a nitrosourea, either BCNU alone or CCNU combined with procarbazine and vincristine (known as the PCV combination). While this treatment has worked for a small minority of people, its 5-year survival rate has been only 2-5%. Alternatives to this traditional treatment regimen are imperative if GBM patients are to have any realistic hope of surviving their disease. Fortunately, new treatments are now being introduced at a rapid rate. But unfortunately, most still are not available outside of clinical trials and there is no consensus about what is the best treatment for this deadly disease.

"There are two general premises to the approach to treatment that will be described. The first of these is borrowed from the treatment approach that has evolved in the treatment of AIDS. Both HIV and cancer involve biological entities that mutate at high rates. This implies that unless a treatment is immediately effective the dynamics of evolution will create new forms that are resistant to whatever the treatment may be. However, if several different treatments are used simultaneously (instead of sequentially, which is typically the case), any given mutation has a much smaller chance of being successful.

"A second general principle is that any successful treatment will need to be systemic in nature because it is impossible to identify all of the extensions of the tumor into normal tissue. Moreover, cancer cells are typically evident in locations in the brain distant from the main tumor, indicating that metastases within the brain can occur, although the great majority of tumor recurrences are within or proximal to the original tumor site. Localized treatments such as radiosurgery may be beneficial in terms of buying time, but they are unlikely to provide a cure. Even if the localized treatment eradicates 99.9% of the tumor, the small amount of residual tumor will expand geometrically and soon will cause significant clinical problems.

"Until recently, the only systemic treatment available has been chemotherapy, which historically has been ineffective except for a small percentage of patients. An important issue, therefore, is whether chemotherapy can be made to work substantially better than it typically does. Also becoming available are new systemic treatments that are much less toxic than traditional chemotherapy. The availability of these treatments raises the possibility that some combination of these new agents can be packaged that is substantially less toxic and yet provides effective treatment based on several different independent principles. Thus, the AIDS-type of combination approach is now a genuine possibility whereas it would not have been ten years ago. Because oncologists have been slow to appreciate the significance of the increased availability of these relatively nontoxic treatments, patients learn about them piecemeal if at all. Thus, patients themselves need to become familiar with these new agents and the evidence available regarding their clinical effectiveness. It is possible, although by no means proven, that some combination of these new agents offers the best possibility for survival.

"Patients may or may not learn about the treatments that will be described from their physicians. To appreciate why this may be, it is important to understand how American medicine has been institutionalized. For most medical problems there is an accepted standard of what is the best available treatment. Ideally this is based on phase III clinical trials. Treatments that have been studied only in nonrandomized phase II trials will rarely be offered as a treatment option, even if the accepted "best available treatment" is generally ineffective. What happens instead is that patients are encouraged to participate in clinical trials. The problem with this approach is that most medical centers offer few options for an individual patient. Thus, even though a given trial for a new treatment may seem very promising, patients can participate only if that trial is offered by their medical facility. An even more serious problem is that clinical trials with new treatment agents almost always study that agent in isolation, usually with patients with recurrent tumors who have the worst prognoses. For newly diagnosed patients this is at best a last resort. What is needed instead is access to the most promising new treatments, in the optimum combinations, at the time of initial diagnosis.

"Physicians rarely will inform a patient about clinical trials being conducted elsewhere. Moreover, the idea that several different agents from separate phase II clinical trials might be combined will be met with great resistance. Patients themselves will therefore need to become informed about what options are available, and which kinds of combinations seem most promising. In addition to the information that will be presented here, other information, especially about which new clinical trials are available, are available elsewhere on this website (address: www.virtualtrials.com ).”

October 30, 2008
Charlotte had her Avastin this morning and will start her Temodar tonight. We will be trying to attend our "Julian Open Studio and Gallery Tour" at our gallery this weekend. Hopefully the nausea caused by the Temodar will be kinder to her this weekend so that she can enjoy her friends. Charlotte right now has a slight headache from the Avastin, but is in very good spirits. We actually have a few people to thank for that.

First, her sister Donna, for always being there at the Avastin treatments, and then bringing laughs and smiles to our faces during lunch. Lunch was at Tio Leo's again today, and thank you again Pete for making it so enjoyable.

And a very special thanks again to Nancy Grossmann, R.N., at Kaiser Permanente for putting up with my never ending questions while Charlotte is getting her Avastin. I can not say enough about how much she means to us.

Another thank you to Dr. Iris Lowe for doing her chiropractic work so that Charlotte is able to continue to walk, and even work, without her being in pain. Walking is so important for patients that are on Avastin to avoid blood clots. One gallery Charlotte wants to visit again is Gallery 21 in Spanish Village in Balboa Park. First, she has so many friends in Spanish Village that she would love to visit again. Dr. Lowe is also currently in a show "Friends of the Chinese Brush" now at Gallery 21 (October 30 -November 17) from 11-4pm . Unfortunately we will not be able to attend the reception this Sunday (4-6pm). But seeing the show and all of her friends in Spanish Village will fit nicely into one of our "walking routines".

Finally, the news about Charlotte's last brain MRI was that her tumor is "stable".

October 20, 2008
Charlotte had her Avastin last Thursday (Oct.16th). We had another appointment with Charlotte's chiropractor, Dr. Iris Lowe, that same evening to help Charlotte with some hip, shoulder and neck problems. Dr. Lowe felt Charlotte's upper vertebra were starting to fuse together, which kept her from walking in an upright position. She came out of there looking, and most importantly, feeling like a new woman.

Charlotte and I worked together at the gallery over the weekend because Mary had a beautiful wedding to put on for a dear friend. It was good to see Charlotte interact with all of the customers, and then find time to work on a small sculpture. Charlotte had a 7am appointment at Kaiser on Monday (Oct, 20th) for her bimonthly MRI. I think there have been some policy changes at Kaiser because now they make you wait about a week for the "official" MRI report if everything is stable. They do a cursory look within 24-48 hours to see if something abnormal appears, and will let you know. But for some reason, as we were leaving because our 20 minutes were up with our neuro-oncologist, I believe she happened to mention that she no longer reads the MRI ahead of time. It's too bad because I think she is, in my opinion, the most qualified to read the MRI. She has seen things that the regular neuro-radiologist has not seen. We fully trust and respect her. I get the feeling that Kaiser is starting to demand some policy changes from their doctors that are not necessarily in the patient's best interest, but I could be wrong. Anyway, I guess we are now in the routine of "no news is good news" for the week. Which, for a proactive husband with a wife with brain cancer, is troubling. I receive emails from other patients and they asked me about this new delay in finding out about their MRI. I told them just what I said above, but that I didn't question it during the visit. I know the clock is running during our appointment, so I told them that I always prioritize my questions before entering.

I must mention, the one true angel since day one, when no other doctors or nurses were around to respond to my urgent emails, etc., is Nancy Grossmann, RN, at Kaiser (Zion). She is the liaison nurse between the study trials and the patients in oncology. She has always returned my phone calls or emails, and helped us in so many ways. Kaiser, give her a pay raise, but don't give her any vacation time! I panic when I know she is not there!

My main job for the last three months has been trying to weigh our options for when Charlotte's tumor returns. As previously mentioned, usually the tumor comes back with a vengeance, and is usually no longer responsive to chemo drugs. Also the Avastin may cloak the tumor so that the MRI looks great, but the clinical condition of the patient declines. Avastin may also make the tumor come back in a more diffuse pattern, so surgery may not be an option. These are just a few of the things that have come out concerning Avastin. I think for Charlotte her best option would try to get into a vaccine trial at UCLA. I've emailed Dr Linda Liau who is charge of the program. The big restriction (besides the cost) is that Dr Liau would need to do another resection on Charlotte for a fresh tumor sample in order to make the vaccine. Due to UCLA's policy and regulations, this surgery can only be done at UCLA, not Kaiser. Our neuro-oncologist thought that the trial could cost us $100,000. Another option for us would be If Charlotte's tumor comes back as an operable mass that could be resected at Kaiser, I could then send the tissue sample to the Weisenthal Cancer Group in Huntington Beach for tumor cell profiling. They would test Charlotte's cancer cells against 20-30 chemo drugs (and combinations) to see which might be most effective. But again that's chemo, and after Avastin, chemo may not be effective. Plus, I've seen it first hand, the body can take only so much chemo. I think the vaccine would be a lot easier for her. Another limiting factor for Charlotte is that most trials want newly diagnosed GBM patients. Charlotte will now be classified as a patient with a recurrent GBM. That limits my options for finding a trial study even further. I don't even know if Charlotte would qualify for the above vaccine trial. There are so many limiting factors to consider (trial cost, trial location, Charlotte's health at the time of reoccurrence, etc.). I just hope Kaiser will give me answers to my questions in a timely manner so that I can further decide what options are actually viable for us.



Charlotte working on "Hope"

October 2, 2008
Charlotte had her Avastin and Temodar today. She had to have a special blood pressure medication (Clonidine) just before the Avastin because her blood pressure was too high. Generally, this has been a month with problems for her, but yesterday she looked magnificent to me. Her normal blood pressure medicine has been increased, and a new blood pressure medicine has been added. She seemed to have her "chemo fog " for all of the month instead of just a week following the Temodar. Her speech and memory have just slightly regressed. But she reads her Mary Oliver, Sarah Teasdale and Walt Whitman poetry out loud every night, along with playing her flute. To me, all of these are inspiring and well done. And of course her sculptures are exquisite. I even had her help me with some Internal Revenue Service forms and some California State Board of Equalization forms. It was sort of a test, since the "math" side of her brain was where most of the GBM (glioblastoma multiforme) was located. She still managed to do a good job.

I have learned you can not just ask her questions in order to find out exactly how she is doing. Some things are obvious, but usually I have to be more intuitive. I remember when she came out of surgery at Kaiser Permanente, the nurse was testing her and asked her who the President of the United States was. She couldn't say "President Bush", but she answered that she could draw his face for the nurse. Today, if she met either Senator Obama or Senator McCain, she would shake their hands, complement them both equally, and tell them each to have a wonderful day. She does that to everyone now. I think that is what aggressive cancer brings out in the truly special people of this world. She has this very strong belief that every person is precious, and needs to be acknowledged. She has always felt this way, but these feelings seem to grow in intensity with each passing day.


Charlotte working on a sculpture last week.

See the archives here.

Please come back to this page for updates on Charlotte's new journey.

Charlotte Mitchell - Poetry In Glass

The love of words inspires artist Charlotte Mitchell to create sculptures mostly out of her favorite material - glass; a wonderfully, colorful medium. However, she augments glass with many other materials such as new ceramics and metal and precious, recycled fire fragments; filling the creations with strength and beauty - inside and out.

Charlotte loves poetry, which has caused her to create her art. She has created beautiful works based on the imagery which fills her mind when reading poetry, song lyrics or other words-well-done. Her inspirations may take her to another part of the world or another time in history. One of the first poems that inspired such works was the last line of "The Summer Day" by Mary Oliver, an unfamiliar poet’s work which Charlotte found taped near the front of a friend’s computer —"Tell me, what do you plan to do with your one wild and precious life..." The imagery of Mary Oliver’s poetry has sent Charlotte’s mind to the forests of Massachusetts, and has lead her straight to Tibet. Mary Oliver is now one of Charlotte’s favorite poets. Walt Whitman’s powerful words has led Charlotte onto the Sea, or onto the Grass. Many sculptures are related to old-time hymn lyrics such as "Amazing Grace", or "old-seeming" lyrics by Sting - "Fields of Gold". All of these go directly to the hearts of people who enjoy beauty or who can regain joy from visions of both the words and sculptures.

One of the largest pieces is called "Something There Is" from Robert Frost’s "Mending Wall". Fire-flashed glass, metal, ceramic faces , and recycled oddments frame a seven-foot wall which wants to crack open as the glass swirls up and out the top of the wall. Built after the 2003 Cedar Fire, this piece has made a tremendous impact on viewers.

Charlotte Mitchell finds the showing of her artwork at the Julian Library both a honor and a privilege. She hopes to show what words and art can do to our lives.

Visit The Mitchell Studio Gallery
4336 Highway 78 (at Wynola Rd), Julian, CA
760-765-1102
Hours will depend on her health, so please call ahead.

It is a bright yellow 110 year-old building
with lots of flare, love, and grace!
Enjoy!
See more photos from the gallery here.