Chemo Agents

What chemotherapy agents does UCLA Neuro-Oncology use to treat patients with a Glioblastoma Multiforme tumor?
Because each patient's treatment plan is unique, therapy normally is dictated by several factors including a person’s age, Karnofsky Score and any previous therapy they have received. Advances in our molecular diagnostics lab is enabling us to better predict what agents will benefit a particular patient group. In general, the following is an overview of agents we used to treat our Glioblastoma Multiforme patients during the past 24 months. This list includes all patients treated at UCLA Neuro-Oncology between 2/9/2005 and 2/9/2007. Period: 2/9/2005 - 2/9/2007-->
• Accutane Hoffmann-La Roche
• AEE788 Novartis
• AMG-102
• Anti Neoplaston
• Avastin (Bevacizumab) Genetech
• BiCNU Carmustine
• Burzynski
• Carboplatin
• CCI-779
• CCNU Lomustine
• Celebrex (Celecoxib)
• Celecoxib (Systemic)
• Cilengitide (EMD 121974)
• CPT -11 (CAMPTOSAR, Irinotecan)
• Dendritic Cell Theapy
• Etoposide (Eposin, Etopophos, Vepesid)
• Gleevec (imatinib mesylate)
• GLIADEL Wafer
• Hydroxyurea
• IL-13
• Iressa (ZD-1839)
• Lapatinib (GW572016)
• LY317615 (Enzastaurin)
• Methotrexate for Cancer (Systemic)
• New castle virus vaccine
• OSI-774
• Poly-MVA
• Procarbazine
• RAD001 Novartis (mTOR inhibitor)
• Rapamycin (Rapamune, Sirolimus)
• RTA 744
• Sorafenib
• Sulfasalazine (Azulfidine)
• Tamoxifen
• TARCEVA (erlotinib HCl)
• TEMODAR Schering-Plough
• Thalomid (thalidomide)
• TransMID Xenova
• Vaccine viii
• Velcade (Bortezomib)
• Vincristine
• Vorinostat (SAHA)
• Zarnestra (tipifarnib)

Combination treatment with Temozolomide and Thalidomide

Combination treatment with Temozolomide and Thalidomideinhibits tumor growth and angiogenesis n an orthotopic glioma model
Abstract. The chemotherapeutic agent temozolomide (TMZ)and the anti-angiogenic agent thalidomide (THD) have bothdemonstrated anti-tumor activity in patients with recurrentmalignant glioma. Combination treatment with TMZ and THDin patients with glioblastoma multiforme (GBM) appears tobe more effective than treatment with either drug alone. Toinvestigate the mechanism of this anti-tumor effect, weexamined the combined effects of TMZ and THD in a ratglioma xenograft model. We found that combination treatmentmarkedly inhibited the growth of tumors that were orthotopicallyimplanted into rat brains. Using proliferating cellnuclear antigen (PCNA) staining, we observed a significantdecrease in cell proliferation in these tumors. CD31 stainingof the microvasculature revealed a significant decrease inangiogenesis. We also found increased apoptosis in treatedtumors by terminal deoxynucleotidyl-mediated deoxyuridinetriphosphate nick-end labeling (TUNEL) assay. We furtherdemonstrated that the expression of angiogenic factors, suchas vascular endothelial cell growth factor (VEGF) and basicfibroblastic growth factor (bFGF), were inhibited by THD.THD also decreased the number of ED1-positive, activatedmacrophages or microglial cells, which produce pro-angiogenicmolecules around the glioma. Taken together, these results
suggest that combination treatment with TMZ and THDinhibits tumor growth via the induction of apoptosis andthe inhibition of angiogenesis in a rat model and may be apromising therapy for malignant gliomas.

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In principle, at least, there are other intriguing approaches. "In some rare cases, people with a viral infection have spontaneous remissions from other types of cancer," says Dr. Juan Fueyo, associate professor of neuro-oncology at M.D. Anderson. "That raises the question, can vi-ruses help fight brain tumors?" Together with his wife, Dr. Candelaria Gomez-Manzano, Fueyo is testing a virus known as Delta-24-RGD that seeks out brain-tumor stem cells. The specially engineered virus infiltrates these cells, then replicates and destroys them. But here's the beauty of the virus. It's incapable of replicating in normal cells, because they have a protein that blocks it. So far, Delta-24-RGD has been tested only in mice, but the results were dazzling. When Fueyo examined the animals' brain tissue, he says, "there was no tumor left—just empty cavities and scar tissue where the tumor had been."
As for Hassenbusch, he's back on the job—and has even taken on additional responsibilities. "I could sit with fuzzy slippers on the La-Z-Boy and watch 'Judge Judy'," he says. "But I guess I'm too dumb to know I should be sick." He's even performing surgery, although he tells patients during their initial consultation that he's had a brain tumor, in case they want another surgeon. So far, no one has—and, in fact, his own experience has made him far more empathetic toward his patients. Even if things don't work out for him in the long run—and the statistics suggest they won't—he says he will have contributed to science. But he's not dwelling on that. Instead he's planning for May 10, 2010, the day that he hopes will mark his five-year survival. He will have a repeat brain scan (like the ones he has every month to monitor his condition), and if the results come back clean, he says, "I will run outside, look up and shout at the top of my lungs, 'Thank you!' " He pauses a moment. "Well, I don't know if I'll actually shout," he says. "But there will be a lot of 'Thank you's." And that could potentially spell hope for a lot of people with a hopeless disease.

newssweek

A few patients have done even better. Among them is David Herbert, 64, of Lincoln, Calif., who is still alive six years after receiving his cancer diagnosis on Dec. 5, 2000. "I'm the poster boy for this drug," he admits. He was also the first recipient of IL13-PE38. But the fact that no other patient had tried it before him didn't make him shy away. "I still had a lot to live for," he says. "Whatever it took, I was going to get through this." Without it, he would likely never have seen his 2-year-old granddaughter, Hope, who was indirectly named for him. Sadly, in August his tumor came back, which he found deeply discouraging. "This isn't a cure," warns Kunwar. "But with just one treatment, we are doubling patient survival." He expects to finish the phase-three trial in early 2007 and, if the results are favorable, have FDA approval within a year.

newwsweek

Long before that day arrives, another drug seems poised to make it to market. Dr. Sandeep Kunwar, a neurosurgeon at the University of California, San Francisco, is working with a drug called IL13-PE38, which is already in phase-three testing. As its hyphenated name implies, it is a two-part drug. The first component—interleukin 13, or IL13—is a naturally occurring immune-system compound. As it turns out, the vast majority of glioblastomas have high levels of receptors for it, but normal brain cells have none. That means that when the drug is injected directly into the brain, it seeks out the tumor cells and binds to their IL13 receptors. (The blood-brain barrier keeps the drug from migrating to other parts of the body that also have these receptors.) The IL13 then serves as a sort of Trojan horse that allows the deadly part of the drug—PE38, a toxin produced by pseudomonas bacteria—to slip inside the tumor cell. "PE38 is a nature-designed killing enzyme," says Kunwar. "It's far more efficient at killing tumor cells than typical chemotherapy." In phase-one testing, 20 percent of patients who received a particular variation of this treatment were still alive three years later, which is "almost unheard of," he says.

newsweek

Hassenbusch may be lucky in another way (if one can call any cancer patient lucky). His cancer appears to be especial-ly responsive to the new chemo drug Temodar, which he's taking as part of his dual therapy. Many patients gain only 2.5 months or so of added survival time from Temodar, because they have a gene that repairs tumor cells almost as fast as the drug can injure them. But that gene is inactive in about 40 percent of patients, who tend to do better. Hassenbusch is among them. Though he is unusual in that he is in the subset of patients who seem to gain the most from Temodar—and who will benefit at all from the vaccine—Heimberger foresees the day when there will be vaccines for all glioblastomas. "There are a dozen other [proteins] that are found only on glioblastomas that could be targeted with vaccines," she says. "One day we will be able to test a patient's tumor cells for these and deliver tailor-made treatments."
Long before that day arrives, another drug seems poised to make it

newsweek cont......

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• Peering Into the Future: Genetic Testing
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• Why Heavy Isn't Healthy
• Health for Life M.D.: Preventing Disease
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• Targeting Needless Breast Biopsies
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• Peering Into the Future: Genetic Testing
• Biomarkers: 'I'm Pretty Optimistic'
• Vitamin D in the Spotlight
• The Dangers of Drug-Resistant Bacteria
• A Six-Foot Lab Rat
• Why Heavy Isn't Healthy
• Health for Life M.D.: Preventing Disease
• Magnets: A New Depression Treatment?
• Targeting Needless Breast Biopsies
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Before and After: At left, his tumor visible on pre-op scan. At right, it's gone after surgery.
But he wasn't content to receive the vaccine alone. He wanted the vaccine plus chemotherapy. The conventional wisdom is that the two are incompatible, since chemo destroys the immune system's white cells—the very thing that a vaccine is supposed to unleash against the cancer. But Sampson had discovered in lab mice that if one waited until white-cell counts bounced back after chemo, then the vaccine could be even more effective in combination with chemotherapy than on its own. "The question was, could we do for Sam what Dr. Sampson had done for those cute little mice?" says Heimberger. Hassenbusch was willing to try—and he became the first person in the country to receive the two treatments on an alternating schedule. He calls it his "double whammy—a one-two punch against the disease."

Before and After: At left, his tumor visible on pre-op scan. At right, it's gone after surgery.
But he wasn't content to receive the vaccine alone. He wanted the vaccine plus chemotherapy. The conventional wisdom is that the two are incompatible, since chemo destroys the immune system's white cells—the very thing that a vaccine is supposed to unleash against the cancer. But Sampson had discovered in lab mice that if one waited until white-cell counts bounced back after chemo, then the vaccine could be even more effective in combination with chemotherapy than on its own. "The question was, could we do for Sam what Dr. Sampson had done for those cute little mice?" says Heimberger. Hassenbusch was willing to try—and he became the first person in the country to receive the two treatments on an alternating schedule. He calls it his "double whammy—a one-two punch against the disease."

Before and After: At left, his tumor visible on pre-op scan. At right, it's gone after surgery.
But he wasn't content to receive the vaccine alone. He wanted the vaccine plus chemotherapy. The conventional wisdom is that the two are incompatible, since chemo destroys the immune system's white cells—the very thing that a vaccine is supposed to unleash against the cancer. But Sampson had discovered in lab mice that if one waited until white-cell counts bounced back after chemo, then the vaccine could be even more effective in combination with chemotherapy than on its own. "The question was, could we do for Sam what Dr. Sampson had done for those cute little mice?" says Heimberger. Hassenbusch was willing to try—and he became the first person in the country to receive the two treatments on an alternating schedule. He calls it his "double whammy—a one-two punch against the disease."

newsweek cont....

declare that he's in remission, he says, "So far it seems to be working. I'm 18 months out, and the tumor hasn't recurred."
That he can make that statement at all is no small feat. Glioblastomas are among the most lethal tumors, because they are resistant to both chemotherapy and radiation. Worse, they send out microscopic tentacles that seed other areas of the brain with individual tumor cells. Even if a surgeon can remove the main mass of a tumor, he cannot possibly excise all these scattered cells. It would be like a chef trying to remove the marbling from a marble cake—and get every last crumb. These additional cells generate new malignancies, sometimes within weeks of the initial operation.
Knowing all that, Hassenbusch underwent surgery at M.D. Anderson on May 25, 2005. He followed up with radiation and chemotherapy. But he had no intention of stopping there. Heck, he was at one of the nation's premier facilities for cancer research, and he was going to look into every possibility. "I made myself into a six-foot-tall lab rat," he says.
After combing the medical literature, he approached Dr. Amy Heimberger, a fellow neurosurgeon at M.D. Anderson, and asked about receiving a new treatment she was testing with Dr. John Sampson at Duke—a cancer vaccine for glioblastoma. The vaccine works by training the immune system to attack cells that have an abnormal receptor on their surface called (take a deep breath) epidermal growth factor receptor variant III, or EGFRvIII. This receptor is found on almost half of glioblastomas and is one of the things that jack up growth signals in them. In phase-two testing, the vaccine has extended patients' median survival to at least 29 months. But the vaccine works only if one's tumor cells carry that specific receptor. Hassenbusch's did.
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Posted By: PJ Ganas (12/7/2006 3:10:20 PM)
Wow! - Great News for you Dr. Hassenbusch - on November 5, 1972, my 51 yr old, very intelligent, very...
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Posted By: Anita Wagner (12/7/2006 3:55:00 PM)
My otherwise healthy mother was diagnosed with 3 inoperable GBMs on 12/20/05, the day after her 75th...
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Posted By: Naomi Lov (12/9/2006 12:15:52 AM)
Sam, you are a posterchild and inspiration to us all. I feel so forunate to have had you help me and...
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newssweek cont.....

In an instant he knew exactly what the next year of his life was going to be like, and it wasn't pretty. "Only 3 percent of glioblastoma patients survive five years—and that's the good news," he says. "More than two thirds die in a year, according to the Central Brain Tumor Registry." Twenty years of medical advances have done little to alter that. But for the first time in decades, scientists are now daring to hope that a series of experimental new therapies could one day meaningfully extend patients' lives—not by weeks, but by months and even years. Hassenbusch became the first person in the country to receive one of them. And though it is too early to declare that he's in remission, he says, "So far it seems to be working. I'm 18 months out, and the tumor hasn't recurred."

newsweek article

Samuel Hassenbusch knows brain tumors. As a neurosurgeon at M.D. Anderson Cancer Center in Houston, he's been operating on them since 1988. But early last year, when he suffered a month long string of persistent headaches, he told himself it was just stress. After all, he was only 51 and fit enough that he'd just completed a charity race for his hospital, combining a 5K run with a 50-mile motorcycle ride—or, as he calls it, "the iron-leg and iron-butt competition." When the thought kept popping into his head that he might have a brain tumor, he quickly dismissed it. "Come on, this is paranoid," he told himself. "Get an MRI to prove it's nothing." Hassenbusch went for the scan on May 10, 2005. When he exited the scanner room, he saw a 17-by-14-inch film posted against a light board—probably some other patient's. Poor guy. Even from 10 feet away, Hassenbusch could see clearly that the patient had a large glioblastoma—the deadliest type of brain tumor. He moved in for a closer look. That's when he saw the name on the top in small white letters—Hassenbusch, Samuel J.

mary francis cancer .com email

Name: Gagbm
Date: 11/29/2006Msg. #: 5 of 8
Duke has a team approach with different doctors holding clinic on different days of the week. If you make your appointment on the same day each time, then you will usually see the same doctor. We have rotated it up a little bit to meet with just about all of the doctors (Reardon, Vrendenburg, Quinn, Dejeardines), except Henry Friedman - he has Wednesdays and that isn't too convenient for us. I don't know how long of a drive from LI to Durham down I-95 & 85. Duke is only 20 minutes North of the Raleigh-Durham airport if that is an option for you. We chose Duke because of its people. They are bright, dedicated, compassionate and will leave no stone unturned to help their patients. They appreciate patients who want to be partners in their care. They also have an arsenal of clinical trials available and will give you the very best they have. I cannot say enough good things about Duke and the Brain Tumor Program. Sloan also has a great reputation and many brain tumor trials available. We visited MD Anderson and were very impressed but felt they were a bit too 'clinical' for us. You start at Duke by contacting Henry Friedman via his pager - expect a call back quickly and at any time (10PM, 8AM Saturday...etc.). Henry speaks very quickly and some feel he comes across as a bit rude as a result - but I can assure you he is most definitely not. Every member of his team is absolutely committed to providing the very best care for their patients. Henry told me when I first contacted him: "Duke will try everything in our power to cure your wife until we are proven otherwise". We couldn't ask for any better than that - nobody has ever dared utter the term 'cure' when it comes to GBM. Some do achieve it, though. Good luck!

mary francis

Screen Name: Geride
Date: 11/29/2006Msg. #: 3 of 7
I have heard you speak of Duke often, who is your doctor there? We are from LI, NY, how difficult would it be for us to get there and who do we get in touch with to get started. My husband is currently on a cellect program of vitamins and healty eating and is doing well, his next mri is Dec 29, but I am so afraid to be hopefull because everytime I am, we fall right back down. So I want to have an alternative plan and start looking into it should this not be working, should they see something even dead cells that might need surgery, there are so many if's with this disease. We have been going to Sloan Kettering but I am somewhat disallusioned with the doctors there. YOu seem to be just a statistic to them. I want a doctor for him that not only is extremely savey with this disease but who also has some sort of compassion for what these people are going thru, and who will listen to our questions and answer them straight forward, not wishy washy and dancing around the bush. I hope and pray that your wife continues to do well and hope that one day I can say my husband is a 18 mo survivor. I will do anything I can to help him get the best possible chance to beat this monster. Be well

Mary Francis

http://www.nwbio.com/clinical_dcvax_brain.php

http://www.nwbio.com/clinical_dcvax_brain.php

Mray Francis Clinical trial results phase 2 glioblastoma treatments

DR. Sampson - Duke

http://www.bioadvance.com/news-press-docs/Alteris_release11.19.04.pdf

http://www.duke.edu/~sampson/

http://www.abc2.org/ga2006_johnsampson.shtml

DR. Sampson - Duke

http://www.bioadvance.com/news-press-docs/Alteris_release11.19.04.pdf

http://www.duke.edu/~sampson/

http://www.abc2.org/ga2006_johnsampson.shtml

Glioblastoma Gene Variations Can Predict Treatment Response

http://www.rxpgnews.com/research/cancer/brain/glioblastomamultiforme/article_2826.shtml

NIH Genetic Analysis

http://www.nih.gov/news/pr/nov2005/ninds-09.htm

Cancer Management

http://i.cmpnet.com/cancernetwork/handbook/pdf/26brain.pdf

Virus Treatments for Cancer

http://www.isracast.com/Articles/Article.aspx?ID=15

Chemo Brain Program

Chemo Brain - Memory Exercises

http://www.cancercompass.com/cancer-news/1,11717,00.htm

To participate
http://www.centerwatch.com/patient/studies/stu95290.html

Ben Willams Email

Dr. Ben Williams
Sent :
Thursday, September 7, 2006 4:13 PM
To :
donnafrancis2006@hotmail.com
Subject :
Re: Message From Virtualtrials Web site!






Inbox


Donna, While statistically patients as old as your mother have a poor prognosis, there are some of them who do reasonably well. There are a number of protocols that are relatively easier to tolerate which look promising. One of these involves a drug called gleevec, in combination with a mild chemotherapy called hydroxurea. The other involves low-dosage temodar on a daily schedule in combination with celebrex. I have no idea what Dr. Friedman might suggest, although his common practice these days is to sequence patients through three chemotherapies, including temodar, CCNU, and CPT-11. But you will need to get the specifics of anything he suggests before I can comment on it. Flaxseed oil is not the idea choice because its anti-cancer effects requires it to be metabolized into other fatty acids, known as DHA and EPA. These are more readily obtained in fish oil. Unfortunately, elderly people often lack some critical enzymes allowing flaxseed oil to be metabolized. Ben P.S.: I will be away for the next week beginning tomorrow.

Ben Williams copy of recent treatments

Attachment :
Treatment_Options-GBM_06__PDF.p (0.18 MB)

survivor story

Enjoying Life Moment by Moment
Bart Byrne
Bart Byrne is a five-year survivor of a glioblastoma, and he thoroughly enjoys the fact that his survival defies statistics. "Not a visit to my neuro-oncologist passes that I don't tell him how pleased I am to be totally screwing up the numbers," Bart said when he gave a talk at the First Unitarian Church of Oakland this past summer. Part of that talk is excerpted here. Bart lives in the San Francisco Bay area with his wife, Leslie, and their daughter, Sarah.

mary francis

As for Dad's chemotherapy regimen, we subscribe to the Dr. Ben Williams' theory of a "cocktail" approach. The idea is to confuse the remnant cancer cells...keep them in retreat and in a state of disarray by throwing different strategies at them over time. Temodar was our first line of defense. Dad took it for 2 cycles. Then we went with CCNU for 2 cycles. Then back to Temodar for 2 cycles again. Now Dad is on his first cycle of CPT-11. All things considered things are great. Dad is approaching one year and so all MRI's show no sign of tumor! We are blessed with every day. As mentioned, Dad continues to work, play golf, and lead a normal life. He is still working to regain his lost power and control in his right leg, but he is making great improvements. Dad did have the standard 6 weeks of radiation done at the Cleveland Clinic during the first cycle of Temodar. We chose to have his chemo administered by one of the finest neuro-oncologists in the field, Dr. Henry Friedman, at Duke University in Durham, NC.

MARY FRANCIS BEN CONTACT BEN WILLIAMS

article: "Treatment Options For Glioblastomas". Click HERE to read it!
Questions?
Send a message to Ben!

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mary francis

Welcome to GBMtrial.com
This website has been designed to provide information about the Phase III clinical trial of Transferrin-CRM107 (Tf-CRM107, proposed trade name TransMIDTM), for the potential treatment of non-operable, progressive and/or recurrent glioblastoma multiforme, a type of brain cancer commonly referred to as GBM. This clinical trial is a research study designed to compare this investigational drug, Tf-CRM107, with the best standard of care treatment currently available.
The content of this site is for informational purposes only. Please consult your doctor to determine if you are an appropriate candidate for this trial.

mary francis

Recommend This MessageReply to This Message
Subject: Glioblastoma-avastinScreen Name: Gennie
Date: 8/31/2006Msg. #: 34 of 36
My husband was diagnosed almost 4 years ago with this dreadful disease. He has been clear for 3 years until the recurrence last 11/05. He is now taking Avastin which is not yet FDA approved. We will know in October if this is working for him. For those who want to have Avastin for Glioblastoma, ask your oncologist to enroll in SPOC program where they will cover expense if the insurance rejects it.

mary francis

http://health.groups.yahoo.com/group/FlaxSeedOil2/message/32640

mary francis

ChemoCoach@ByMySide.chtah.com

MARY FRANCIS

ChemoCoach