DEALING WITH AN AGGRESSIVE BRAIN TUMOR

Last Update: October 15, 2007
(Created April 18, 2007)


ANNOUNCEMENT! - NEW BRAIN TUMOR ONLINE GROUP:
Yahoo! Brain Tumor Treatments Research (brain-research)

Contents:
1. Website Purpose, Limitations, and Disclaimer
2. Resources
3. General Considerations
4. Treatments Overview
5. Conventional Treatments
6. Complementary/Alternative Medicine (CAM)
7. Related Medical Problems


1. WEBSITE PURPOSE, LIMITATIONS, AND DISCLAIMER

(PLEASE READ THIS FIRST!)

This website was developed by Irfan Alvi. I am not a physician or any other kind of health care professional. My professional background is in engineering. My biomedical background consists mainly of several university biomedical courses; information obtained from reading many books, papers, and websites; information provided by physicians; information provided by many brain tumor patients and caregivers (thank you!); and my personal experiences in dealing with health issues.

This website exists because of, and is dedicated to, my mother, who passed on in August 2007 from a brain tumor, specifically Glioblastoma Multiforme (GBM). The information in this website therefore pertains primarily to adult GBM, although much of it may also apply to other malignant primary brain tumor types and to children. Much of this information definitely will not apply to benign tumors, nor to secondary brain tumors, which are tumors that develop outside the brain and then travel (metastasize) to the brain. If you are dealing with a tumor other than adult GBM, I recommend that you first research information specific to your tumor type, and then use the information in this website only secondarily and selectively.

None of the information in this website should be considered authoritative medical advice. Moreover, much of what is provided here consists of my personal impressions and opinions. The main purpose of this website is to help others save precious time, especially those new to dealing with a brain tumor. I also hope that outcomes will be improved, in terms of both quantity and quality of life. However, I can not accept any liability for the information and opinions offered here. Think of this website as notes to myself, which others are welcome to review.

Please also do not rely solely on this website for information or opinions. This website is by no means comprehensive or complete, nor is it intended to be. It's more of a starting point to begin learning about the topics mentioned. Please be aware that some topics important to your situation may not even be mentioned in this website. The provided links and listed resources will help you learn more.

In general, I recommend cross-checking information by using multiple sources, and getting multiple opinions, both within conventional medicine and outside of it, in order to help form your own opinions and make your medical decisions. That is the process I personally followed, and this website summarizes the results of that process.

Corrections and contributions to the website will be greatly appreciated, and can be provided by contacting me at the following email address:

iaa@comcast.net

Given these limitations and disclaimers, how comfortable should you be in making use of this website? That has to be your decision, but what I can say is that this website has been developed in good faith, has no commercial interests or affiliations, no funding has been solicited or recieved for its development, and I have tried to be thorough. I have also tried to convey my degrees of uncertainty with appropriate word choice throughout the website.


2. RESOURCES

2.1 Useful Websites

Medline Plus Brain Cancer (portal to access a wide variety of information)
National Cancer Institute (NCI) Brain Tumor Page (somewhat superficial, but a starting point)
Virtual Trials Home Page (extensive information, but limited for CAM)
Brain Tumor Dictionary (from Virtual Trials)

List of Brain Tumor Treatments (Many items haven't been updated since 2005, and some available treatments aren't on the list)

Finding a Clinical Trial (via Virtual Trials)
Finding a Clinical Trial (via NIH)

PubMed (to search the medical literature)

Treating Glioblastoma (under development; similar in spirit to this website)
Life Extension Foundation (LEF) (source of supplements and related research)
MD Anderson CAM (useful but conservative resource; don't rely on any single source for CAM)

The Cancer Tutor (presents CAM options beyond diet and supplements)
Alternative Cancer Treatments (presents CAM options beyond diet and supplements)
Steve Dunn's Cancer Guide (good general information, but not focused on brain tumors)

PDR Health (information on drugs, supplements, and herbs; see links at left middle of page)
Yahoo! Health (good general source of medical information)


2.2 Online Groups

Yahoo! Brain Tumor Treatments Research Group (NEW! - focused on researching available and emerging treatments)
Yahoo! Brain-Temozolomide Group (focused on conventional medicine; biased against CAM)
Yahoo! Brain Tumor Supplements Group (focus on nutritional supplements for brain tumors)
Yahoo! Ruta-6 Research Group (technical discussion of Ruta)
Yahoo! Ruta6 Support Group (general discussion of Ruta)
Yahoo! Cancer Cured Group (focus on alternative cancer treatments)
Yahoo! Pediatric Brain Tumors Group (focus on pediatric brain tumors)
BRAINTMR List (brain tumor discussion group)


2.3 Papers to Read First

Treatment Options for Glioblastoma and Other Gliomas, by Ben Williams, PhD (provides a relatively up to date summary of many treatment options, although not all categories of CAM treatments are included)

Brain Tumor Guide for the Newly Diagnosed, by the Musella Foundation (provides general information related to dealing with a brain tumor)

The Essential Guide to Brain Tumors, by the National Brain Tumor Foundation (provides general information related to dealing with a brain tumor)

Glioblastoma Multiforme: Nutritional and Botanical Approach, by Jeanne M. Wallace, PhD, CNC (describes dietary and nutritional supplement approaches for brain tumor treatment; email me to get a free copy of the paper, or download from the 'Files' section of the Brain Tumor Treatments Research Group)

Treatment Options for Glioblastoma, by Marc Chamberlain, MD (relatively technical and describes various treatment options offered by conventional medicine)


2.4 Other Useful Papers

Cancer as an Evolutionary and Ecological Process, by Merlo et al (provides considerable insight into tumor evolution and treatment strategy)

Glioblastoma Multiforme - Past, Present, and Future, by Andrew Lassman, MD and Eric Holland, MD, PhD (technical but short, and the conclusion is insightful)

Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Newly Diagnosed Glioblastoma, by Roger Stupp, MD et al (one of the key Temodar papers; includes survival curves)

Glial Tumors: The Current State of Scientific Knowledge, by Nicholas Butowski, MD and Susan Chang, MD (good overview at a good technical level)

Recent Advances in the Treatment of Malignant Astrocytoma, by David Reardon, MD et al (overviews tumor biology and treatment options)

Neurobiology of Brain Tumors, by Jeffrey Bruce, MD (a bit technical, but provides useful details regarding the biology of brain tumors)

Changing Paradigms: An Update on the Multidisciplinary Management of Malignant Glioma, by Roger Stupp, MD et al (an overview of basic conventional treatment options, with some discussion of emerging treatments)

Malignant Glioma: Genetics and Biology, by Maher et al (long and technical, and also a few years old [2001], but perhaps still useful)

Therapeutic Advances in the Treatment of Glioblastoma: Rationale and Potential Role of Targeted Agents, by David Reardon, MD and Patrick Wen, MD (a relatively detailed and up to date discussion on emerging targeted treatments)

Targeted Molecular Therapy of GBM, by Paul Mischel, MD and Tim Cloughesy, MD (another rather technical discussion of targeted treatments)

Targeting Angiogenesis with Integrative Cancer Therapies, by Donald Yance, MH and Stephen Sagar, MD (a technical discussion on the use of supplements and herbs for treatment of cancer, focusing on anti-angiogenesis)

A Novel Approach to Cancer Treatment: Botanicals that Inhibit Angiogenesis and/or Enhance Nonspecific Biological Immune Response, by Donald Yance, MH (a technical discussion on the use of supplements and herbs for treatment of cancer, focusing on anti-angiogenesis)


2.5 Recommended Books

The books listed in this section can generally be found at Amazon.com, and many are probably available at your local bookstore. To review and order books from Amazon, see Amazon Book Search.

The following are key books related to brain tumors, written for patients and caregivers, focused on conventional medicine:

- "100 Questions & Answers about Brain Tumors" by Virginia Stark-Vance, MD, 2004 (convenient resource for FAQs)
- "Living with a Brain Tumor" by Peter Black, MD, PhD, 2006 (up to date, informative, and well organized)
- "Brain Tumors: Leaving the Garden of Eden" by Paul Zeltzer, MD, 2004 (good information, but the format isn't my favorite)
- "Brain Tumors: Finding the Ark" by Paul Zeltzer, MD, 2006 (good information, but the format isn't my favorite)

The following books address cancer treatment using diet, nutritional supplements, and herbs:

- "Surviving 'Terminal' Cancer" by Ben Williams, PhD, 2002 (HIGHLY recommended, and complements his paper noted above)
- "How to Prevent and Treat Cancer with Natural Medicine" by Michael Murray, ND et al, 2002 (a key resource)
- "Herbal Medicine, Healing, & Cancer" by Donald Yance, MH, 1999 (another key resource)
- "Natural Strategies for Cancer Patients" by Russell Blaylock, MD, 2003 (a key resource by a neurosurgeon with over 20 years experience treating cancer patients using diet and supplements)
- "Beating Cancer with Nutrition" by Patrick Quillin, PhD, RD, CNS, 2005 (a key resource, and includes a nice one-hour audio CD)
- "Beating Cancer with Natural Medicine" by Michael Lam, MD, 2003 (useful information, but could be organized better); see
Dr. Lam's Website
- "Natural Compounds in Cancer Therapy" by John Boik, 2001 (vast amount of valuable information; see Page 7)
Description PDF
- "Cancer & Natural Medicine" by John Boik, 1996 (complements his other book)
- "Evaluating Alternative Cancer Therapies" edited by David Hess, PhD, 1999 (good chapters on various treatment philosophies)
- "The Natural Pharmacy" by Alan Gaby, MD, 2006 (best single reference on supplements and herbs, but don't rely on just one source)
- "A-Z Guide to Drug-Herb-Vitamin Interactions" by Alan Gaby, MD, 2006 (as the title states)
- "Disease Prevention and Treatment" by Life Extension Media, 2003 (contents available free at LEF website; see link above)

The following books emphasize CAM treatments other than the usual dietary and supplement measures:

- "Cure Your Cancer: Your Guide to the Internet" by Bill Henderson, 2003 (HIGHLY recommended; presents many treatment options you won't hear about elsewhere, and has many links to websites)
- "Outsmart Your Cancer: Alternative Non-Toxic Treatments that Work" by Tanya Harter-Pierce, 2004 (describes a variety of treatment options, many of which are controversial)


2.6 Recommended Audiobooks

While books can provide valuable information, brain tumor patients and caregivers usually lack time to read them, and health issues often make it difficult for patients to read even if time is available. Audiobooks are a good solution to address these difficulties since they can be listened to while getting ready in the morning or while driving, and it takes much less time to get through an audiobook as compared to a printed book. Audiobooks are often abridged, which can be beneficial since many printed books are unnecessarily long and the abridgement often cuts out the "fluff." This efficiency allows audiobooks to be gone through more than once, which helps information sink in. Ranked roughly from highest to lowest priority, the following are several audiobooks which I've found helpful, nearly all of which are available from Amazon.com:

- "The Anatomy of Hope: How People Prevail in the Face of Illness" by Jerome Groopman, MD, 2004 (balanced and inspiring)
- "Alternative Medicine for Dummies" by James Dillard, MD and Terra Ziporyn, PhD, 1999 (short but very good, and not just for dummies)
- "Eat to Beat Cancer" by J. Robert Hatherill, PhD, 1998 (very good discussion on diet and supplements)
- "Miracle Cures" by Jean Carper, 1997 (short but good introduction to nutritional supplements; not focused on cancer)
- "Dr. Rosenfeld's Guide to Alternative Medicine" by Isadore Rosenfeld, MD, 1998 (good and extensive introduction to alternative medicine, although some conclusions are obsolete or debatable)
- "Ultra-Prevention" by Mark Hyman, MD and Mark Liponis, MD, 2003 (excellent and thorough discussion on nutrition; relevant but not specific to cancer)
- "Eating Well for Optimum Health" by Andrew Weil, MD, 2000 (excellent and thorough discussion on nutrition; relevant but not specific to cancer)
- "Reinventing Medicine: Beyond Mind-Body to a New Era of Healing" by Larry Dossey, MD (nicely describes the possible role of spirituality/prayer in healing)
- "Return to Wholeness: Embracing Body, Mind, and Spirit in the Face of Cancer" by David Simon, MD, 2000 (as the title says; emphasizes mind-body medicine)
- "The Transformed Cell: Unlocking the Mysteries of Cancer" by Steven Rosenberg, MD, PhD, 1992 (a valuable look into the cancer research process)
- "Timeless Healing" by Herbert Benson, MD, 1996 (good discussion of mind-body medicine)
- "Getting Well" by Carl Simonton, MD, 1987 (focused on mind-body medicine)
- "A Guide to Alternative Self-Healing Techniques for Cancer" by William Collinge, MPH, PhD, 1998 (focused on mind-body medicine)
- "Your Body's Natural Wonder Drug: Melatonin" by Russel Reiter, PhD, 1995 (a bit dated, but relevant because of the value of melatonin for brain tumor treatment)
- "Healing Lessons" by Sidney Winawer, MD, 1998 (a beautiful telling of a personal cancer journey, but some may find it emotionally distressing)
- "Biology on Tape: Human Anatomy & Physiology, Parts I and II", by David Gantt, PhD, 1995 and 1997 (a very dense review, thus not suitable as an introduction)
- "Biology on Tape: Understanding the Cell" by AudioText, 1994 (a very dense review, thus not suitable as an introduction)


2.7 Recommended Videos

The following are several videos I've found useful which are available free online:

Brain Tumor Survivor Stories (about 50 minutes)

Histopathology - GBM (only 2 minutes, but very informative)
Histopathology - GBM (only 6 minutes, but very informative)
Histopathology - Astrocytoma (only 3 minutes, but very informative)
Histopathology - Oligodendroglioma (only 2 minutes, but very informative)
Histopathology - Meningioma (only 3 minutes, but very informative)
Histopathology - Medulloblastoma (only 3 minutes, but very informative)
Histopathology - Brain Hemorrhage (only 2 minutes, but very informative)

Integrative Medicine, by Evan Ross, LAc, DOM (about 31 minutes, good introduction to CAM for brain tumors, but not much detail)
Nutritional & Herbal Strategies to Complement Conventional Brain Tumor Treatments, by Jeanne Wallace, PhD, CNC (about 40 minutes, focusing on diet and supplements)
Food as Medicine, Part 1, by Jerry Brunetti (about 90 minutes, focusing on diet)
Food as Medicine, Part 2, by Jerry Brunetti (about 90 minutes, focusing on diet)

Other Videos at Virtual Trials

For those interested in a university-level introduction to biomedicine, I suggest considering the following four video courses from The Teaching Company (be sure to get them at the "sale" price). The first two courses are quite lengthy and are not focused on cancer, so they will probably not represent the best use of time for those currently dealing with an aggressive brain tumor. The third course is shorter, addresses many health problems faced by brain tumor patients, and has five lectures specifically on cancer, so it may be more helpful. However, the organization and clarity of the presentation is mediocre, with details often being presented without sufficent explanation to make them useful, and there are some errors in the content. I therefore recommend this third course only to those who have a strong interest in this type of information and who will be using multiple sources. The fourth course focuses on the brain, but doesn't address brain tumors, so its value is mainly for understanding general brain anatomy, function, and deficits.

Biology: The Science of Life, by Stephen Nowicki, PhD (prior general science background is helpful but not vital)
Understanding the Human Body: An Introduction to Anatomy and Physiology, by Anthony Goodman, MD (prior biology background is not required)
The Human Body: How We Fail, How We Heal, by Anthony Goodman, MD (prior biomedical background would definitely be helpful, but isn't mandatory)
Understanding the Brain, by Jeanette Norden, PhD (prior biomedical background would be helpful, but isn't mandatory)


3. GENERAL CONSIDERATIONS

3.1 Prognosis, Statistics, and Hope

The "prognosis" for GBM and many other types of brain tumors is currently not good, but there are good reasons not to give up hope. When interpreting statistics, the following points should be considered:

Several survivor stories can be found here: Survivors. Also see a video of survivors telling their stories, as well as the experience of Evan Ross. As further evidence that cure of GBM is indeed possible, see a recent Canadian paper.

Survival statistics can be found for various types of brain tumors at the UCLA Neuro-Oncology Statistics website. These statistics are based specifically on UCLA's experience, and they are generally more encouraging than other statistics found in the broader literature. Some people may find reviewing statistics to be discouraging, so consider not looking at them. If you do choose to review them, please keep all of the above points clearly in mind.

The following short essay is also worth reading: The Median Isn't the Message.


4. TREATMENTS OVERVIEW

4.1 Overview of Treatment Options

The available treatments for brain tumors can be broadly categorized as either "conventional" medicine or "complementary/alternative" medicine (CAM).

CONVENTIONAL MEDICINE

The main standard treatment options for brain tumors currently offered by conventional medicine are:

- Surgery, to physically cut out as much of the tumor as possible
- Radiation therapy, which usually involves directing external radiation beams at the tumor
- Chemotherapy, which involves drugs to "poison" the tumor

The majority of patients recieve all three of these treatment types, and usually in the sequence listed. Chemotherapy is sometimes given during radiation as well as after it (see Section 5.3).

The main advantage of these treatments is that they are based on considerable medical research and experience, and are administered under the care of physicians. If desired, this gives the patient and caregivers the option of leaving treatment decisions largely in the hands of the physician (though I don't recommend that).

The main disadvantage of these treatments, which is a serious disadvantage, is that currently they are not highly effective for most patients, although a minority of patients do benefit significantly. Unfortunately, it is currently difficult to predict which patients will benefit significantly from a given treatment, although some progress is starting to be made in identifying them through development of various testing methods (eg, MGMT testing). Some of these tests require tumor tissue specimens obtained during surgery, so be sure to have arrangements in place to obtain and test tissue specimens while the opportunity is available.

A further disadvantage is that conventional treatments usually involve significant risks and side effects, thus often lowering quality of life, sometimes quite dramatically. When such treatments are pursued too aggressively for a given patient, they can also adversely impact survival, either directly or by weakening patients to the extent that they can't tolerate and/or respond to further treatments.

EMERGING TREATMENTS WITHIN CONVENTIONAL MEDICINE (IMPORTANT!)

A variety of promising newer treatments are emerging within conventional medicine which offer the potential to greatly improve survival, while having lower risks and side effects than current treatments. They will be described as this website is updated.

Meanwhile, to keep up with such treatments, I recommend joining online brain tumor groups such as those listed in Section 2.2, reading the paper by Ben Williams, PhD listed in Section 2.3 (this paper is updated annually), subscribing to the
Brain Tumor Daily News Blast and BrainLife Email Alert Service , and periodically checking Glioblastoma News. You can also use Google Alerts to do automated searches using keywords such as "glioblastoma," "temozolomide," "CPT-11," etc. For some recent information, also see selected data and abstracts from ASCO 2007.

One particular newer treatment which has shown promise as an alternative to standard treatments, and is therefore definitely worth looking into, is
CPT-11 (irinotecan) & Avastin (or just Avastin by itself).

COMPLEMENTARY/ALTERNATIVE MEDICINE (CAM)

Some key types of CAM treatments are:

- Good diet
- Highly modified diets
- Nutritional supplements
- Herbal medicines
- Homeopathic remedies
- Other treatment agents classified as "dietary supplements" (eg, Protocel)
- Regular exercise
- Positive outlook and attitude
- Meditation, hypnosis, and guided imagery
- Spirituality and prayer

The main advantage of CAM treatments is that, when used properly, many of them can probably provide survival benefits, possibly substantial benefits, while having limited risks and side effects. Moreover, such treatments can enhance general health and can offset side effects due to conventional treatments, thus enhancing quality of life.

The main disadvantage of such treatments is that most physicians are uninformed about them, and are therefore unable to guide patients in using them, and may even discourage patients from using them due to unfounded bias. Also, CAM treatments are not usually covered by health insurance, although many of them are relatively inexpensive, especially given what is at stake. Finally, some CAM treatments, especially those involving compounds taken into the body, can have adverse effects if impure or not used properly, although generally they are still much safer than conventional treatments such as chemotherapy.

Because CAM treatments usually can not be effectively patented, CAM research is generally underfunded and few Phase III clinical trials have been completed and few are on the horizon. This makes it difficult to reach definite conclusions about the effectiveness or safety of most CAM treatments. However, various Phase I and II trials have been completed, and a variety of anecdotal, in vitro (cell culture or test tube), animal, and non-US clinical data provides growing and converging evidence supporting use of CAM for cancer patients. The references listed in this website describe much of this evidence.


4.2 Treatment Strategy

In my opinion, if a genuinely promising clinical trial is available (see the clinical trials links in Section 2.1), it should be given serious consideration. This will usually involve carefully examining both the theoretical rationale for the trial, as well as the results of related prior clinical trials and preclinical studies. Such examination is important because the majority of clinical trials do not provide substantially better results than the existing standard treatments, and sometimes the treatments available through trials are not even as effective as the existing standard treatments. Therefore, "trial" does not always mean better treatment and one should not enroll in a trial simply because it is offered. Fortunately, truly better treatments may be available through trials in coming months and years. CAM treatments can be used in conjunction with clinical trials, and I believe it is generally desirable to do so, provided that one can be adequately confident that the CAM treatments will not adversely interact with the treatment used in the clinical trial.

If a promising clinical trial is not available, in my opinion, based on the treatments I've reviewed to date, the best treatment strategy is likely to be a multifaceted and highly proactive approach which combines multiple conventional treatments with multiple CAM treatments, sometimes referred to as a "combination treatment" or "treatment cocktail." The desire to be proactive should also be weighed against a patient's age, general health, attitude, quality of life considerations, and other personal desires.

Since cancer cells can use a variety of pathways to survive and proliferate, the idea behind the combination/cocktail approach is to simultaneously cut off as many of these pathways as possible, and also to strengthen the body's capacity to identify and eliminate cancer cells, especially through modulation of the immune system. To accomplish this, it is desirable to select treatments, both conventional and CAM, which work by different mechanisms and thus block different pathways.

Specifically with regard to supplements, a related point is that Temodar and many other chemotherapy drugs work as alkylating agents, whereas supplements generally work by other mechanisms. This suggests that these chemotherapy drugs and supplements may complement each other synergistically.

However, it should be noted that when combining treatments in a cocktail approach, there is a risk that treatments will adversely interact in ways that (a) reduce overall effectiveness of the treatment due to interference between treatments and/or (b) increase side effects or create new side effects due to "overlapping toxicity." The risk of such adverse interactions can't be ruled out (see Section 6.5), but generally speaking, if the combination of treatments is chosen carefully, in my opinion the potential for beneficial synergistic interaction would likely outweigh the risks.

Since only a minority of patients do well using only current standard conventional treatments, personally I don't favor relying on these conventional treatments alone. Similarly, I'm not currently convinced that it's prudent to rely on CAM alone. However, I've by no means researched all the available CAM options, and some would argue that benefit from CAM treatments is greatly reduced if they are used after conventional treatment, especially if the convetional treatment has already failed. Therefore, if you've thoroughly researched a particular CAM option and find the evidence compelling enough to solely rely on it, don't let my lack of knowledge deter you from doing so. Since there are certainly various CAM treatments which are claimed by some to be quite effective by themselves, I do plan to explore such treatments in the future, but this is likely to be a lengthy process.

A respected oncologist with a sophisticated and individualized integrative approach to cancer treatment, combining both conventional medicine and CAM, is Keith Block, MD, located in Illinois. The following links provide further information regarding his cancer center and approach to treatment:

Block Center for Integrative Cancer Care
Block Center Resumes
Integrative Cancer Care Approach (see additional small links at right of page)
Papers by Keith Block, MD

Another respected neuro-oncologist, recognized for his hopeful and proactive approach to treating brain tumors, as well as his dedication to his patients, is
Henry Friedman, MD at Duke University, which is regarded by many as the leading brain tumor center on the US east coast.


4.3 Ending Treatment and Preventing Tumor Recurrence

Assuming that treatment has been effective, with clear MRI scans for many months and lack of symptoms, the question of when to stop treatment arises.

My understanding is that once a patient has had a tumor, there will be a non-negligable risk of recurrence for many years. One main reason is that MRI scans and other scans depict the brain at a "gross" level, not a microscopic level, whereas only one surviving tumor cell can be sufficient to eventually regrow a tumor. In this regard, the cells in a tumor are usually diverse, and a particular treatment or combination of treatments may eliminate nearly all tumor cells, but some may be resistant and still survive the treatment. To quantify this, consider that most visible tumors contain at least a billion cells, and eliminating 99% of them would still leave at least 10 million cells.

With all of this in mind, with regard to conventional treatments, I believe that the decision of when to end treatment needs to be made on an individualized basis considering factors such as type of tumor, aggressiveness (or "grade") of tumor, treatment history, history of the response to treatment (including past tumor recurrences), risk that allowing a treatment "gap" will allow the tumor to evolve into a form which becomes resistant to further treatment, possible side effects of continued treatment, general health, age, and personal circumstances and desires. In general, it seems sensible to extend the duration of treatment if the treatment has limited side effects, although the usually small risk that the treatment will cause a new cancer needs to be considered.

It is also helpful to recognize that some combination of genetic and life history factors resulted in the tumor in the first place, and many of these factors may still be in place after treatment has been successful. To address these factors and help prevent tumor recurrence, adopting a proactive cancer prevention strategy seems sensible. Such a strategy would involve the CAM measures described in Section 6, with the understanding that supplements used for cancer treatment could be continued for cancer prevention, although possibly at lower dosages.

There appears to be significant evidence, include several anecdotes that I've personally verified, which indicates that a cancer prevention strategy can help to keep a microscopic tumor from growing without necessarily eliminating it, whereas discontinuing cancer prevention could allow the tumor to recur in an agressive form which is very difficult to treat. I know of several cases where people were taking an aggressive supplements protocol for years, with clear MRI scans, then they either stopped the supplements or substantially reduced their amounts, and a few months later their tumors aggressively recurred. Therefore, in my opinion, the most prudent approach is to assume that once one has been a tumor patient, one is always a tumor patient and must remain vigilant -- that would especially include NOT stopping or reducing supplements unless there is very strong evidence that the tumor has been 100% eliminated.


5. CONVENTIONAL TREATMENTS

5.1 Surgery

The goal of surgery is to remove as much of the tumor as possible. With a tumor type such as GBM, it is generally not possible to remove 100% of the tumor, since the tumor has projections which extend into the surrounding normal tissue. Removing as much tumor as possible ("resection" or "debulking") is still beneficial to improve survival, but an overly aggressive approach can backfire since it involves greater risk of damage to the normal tissue. Such damage can result in a variety of neurological deficits which can impact quality of life. In short, be aggressive, but be careful.

Seek recommendations to find the best available neurosurgeon, and look specifically for experience in removing brain tumors, not just general neurosurgery experience. Your neuro-oncologist may be a good source of recommendations.

If you are told by a neurosurgeon that a tumor is inoperable (can't be safely accessed or removed), seek other opinions since some surgeons can successfully perform operations others would shy away from.

The bottom line is that neurosurgeons aren't all equally good, and it does make a difference, so get yourself a good one.


5.2 Radiation Therapy

The type of radiation therapy most commonly administered to patients consists of external radiation beams focused on the tumor plus a surrounding "margin" of normal tissue about 1 inch thick. The radiation is normally administered 5 days a week for 6 weeks, with each treatment lasting about 15 minutes. The chemotherapy drug Temodar (see Section 5.3 below) is often administered daily while undergoing radiation therapy. Other types of radiation therapy are also available, which will be described as this website is updated.

Radiation provides a survival benefit usually on the order of months, and can provide even greater benefit when used as part of an aggressive treatment plan. However, the benefits of radiation should be weighed against the possibility of side effects, many of which can seriously impact quality of life both short-term and long-term. Many of the potential side effects can occur weeks and months, even years, after finishing the treatment. As patients live longer, these long-term side effects will become an increasingly significant issue.

Because the radiation is directed at the brain, rather than another less "vital" part of the body, the side effects can be serious and may include general cognitive impairment, memory impairment, other more specific impairments of mental and physical function (depending on the locations of the tumor and the radiation targeting), fatigue, and hair loss, among others. Radiation can also cause skin damage, and Murray et al (2002) indicate that the nutritional supplement quercetin (see Section 6.3), at 200 to 400 mg daily, may help to protect against such damage. Radiation can even cause a new tumor to form, but that is relatively rare.

Because of these potential side effects and their impact on quality of life, I recommend that brain tumor patients carefully consider whether radiation makes sense for them. I don't want to necessarily steer anyone away from using radiation, but I think it's important to mention the potential side effects since the decision regarding whether to proceed with radiation is usually made just a few weeks after surgery, when patients are early in the process of exploring treatment options and still have much to learn.

For more information regarding radiation, see ASTRO's
brochure , but keep in mind that this source is likely to be biased, tending to somewhat overstate benefits and downplay risks.


5.3 Chemotherapy

The most commonly prescribed chemotherapy for GBM is temozolomide (Temodar or Temodal). Other chemotherapy drugs are also available both through clinical trials and outside trials, and will be described as this website is updated. Meanwhile, please see other links in this website to get more information about them.

When Temodar is given during radiation therapy, it is usually given daily for 42 days. After a "break" of about 4 weeks, Temodar is then continued in cycles.

The most common schedule consists of 6 cycles, with each cycle consisting of 5 days on Temodar followed by 23 days off Temodar (5/23). Some neuro-oncologists favor continuing beyond 6 cycles provided that the Temodar is proving effective and the side effects are tolerable. In my opinion, this approach is reasonable. However, the potential benefits of long-term Temodar need to be weighed against the risk that the Temodar might eventually cause a new cancer, for example leukemia or lymphoma. Temodar was indeed found to cause various cancers in rats using doses which were not particularly high (see Temodar package insert, page 7, using link below). However, I'm not aware of any data which helps quantify this risk specifically in humans. I suspect that the risk is relatively low, particularly compared to the risk that the original tumor will grow.

Other Temodar schedules, sometimes referred to as "metronomic" and "dose dense" schedules, are also being studied and used by patients. They include continuous daily dosing, 21/7, 14/14, and 7/7. Several studies indicate that these alternate schedules may improve survival, possibly substantially, but there is conflicting information regarding the risks and side effects as compared to the 5/23 schedule, particularly with regard to blood counts. A recent study presented at ASCO 2007 (see link in Section 4.1) showed promising preliminary results for the 7/7 schedule, but the study is still in progress. For patients whose general health (other than the brain tumor) is good, and who will have blood tests taken at least once a week, I lean somewhat towards favoring the alternate schedules. For patients in poorer condition, personally, I'm undecided regarding whether the standard or alternate schedules seem preferable.

With Temodar, the main potential side effects are reduced blood counts, with their associated consequences (increased risk of bleeding, increased risk of infection, fatigue, shortness of breath, etc.), as well as nausea, vomiting, and constipation. Many of these side effects can be managed with monitoring and other drugs.

In severe cases, Temodar and other chemotherapies can damage bone marrow enough that blood transfusions are required until the bone marrow recovers. In relatively rare cases, the bone marrow damage is so extensive that it never recovers and blood transfusions are required for the remainder of the patient's life.

Considering these risks and side effects, it is extremely important that the proper dosage of chemotherapy is taken, and patients should double check this themselves. Dosage of Temodar can be checked here:
Dosage Calculator.

For more information on Temodar, see Temodar.


6. COMPLEMENTARY/ALTERNATIVE MEDICINE (CAM)

6.1 Diet

Diet is in many ways a foundation for CAM, and my research indicates that the following diet is quite likely to be helpful for cancer patients, as well as for cancer prevention and general health among everyone else (I personally follow this diet fairly closely):

- Eat plenty of fresh whole vegetables, preferably organic, in a variety of colors, favoring darker colors, several servings per day. Avoid overcooking them. Many vegetables can be eaten raw, and steaming is also a good option for most vegetables. Juicing is also an option to consider.

- Eat plenty of fresh whole fruits, preferably organic, in a variety of colors, favoring darker colors, several servings per day. Eating fruits at the end of a meal will usually help prevent surges in blood glucose (sugar) levels.

- Among animal proteins, emphasize fish, but avoid fish containing mercury or other toxins; salmon (non-farmed), mackerel, herring, and sardines are good choices. Chicken or turkey is second best after fish, and organic is preferable. Beef is best avoided, especially grilled beef or overcooked beef. Organic beef is much more acceptable than non-organic.

- Drink plenty of water, say 6 or more glasses per day, but don't drink too much with meals.

- Potatoes have limited nutritional value, and tend to increase blood sugar, so consider avoiding them. Sweet potatoes appear to be better than white potatoes.

- There are varying opinions regarding grains. A compromise would be to consume them in moderation. This applies to rice and bread also, with whole grain products being preferable. "Enriched" products should be avoided.

- There are varying opinions regarding dairy products. A compromise would be to consume them in moderation. Soy milk is a good substitute for regular milk. There are also good substitutes available for butter.

- Avoid products containing saturated fats and partially hydrogenated fats.

- Avoid salted, smoked, pickled, and processed foods, including foods containing preservatives.

- Avoid sweets and anything else containing raw or refined sugars.

- Avoid artificial sweeteners such as saccharin and aspartame. However, stevia may be a reasonable option.

- Avoid soft drinks.

- Avoid anything else than seems to be "junk food."

- AVOID GRAPEFRUIT PRODUCTS! Through their effect on liver enzymes, they can adversely interact with drugs and other compounds such as nutritional supplements.

- As your diet is changed, be on the lookout for possible allergic reactions. They are generally uncommon, but they do occur.

While good diet is important and can make a big difference, it is also vital that cancer patients get enough calories, even if that means compromising on the quality of their diet. A mediocre diet is better than no diet.

The following section focuses on nutritional supplements, but the discussion there on the work of Jeanne Wallace, PhD, CNC also relates to diet.


6.2 General Comments on Nutritional Supplements & Antioxidants

Personally, unless there are unusual circumstances, I generally favor use of supplements by cancer patients. In my opinion, there is good evidence that supplements can work together synergistically and provide significant benefits. For this reason, my impression is that, in general, the more supplements one takes, the better, since this will increase the chance of inhibiting more of the tumor's survival pathways, ideally all of them.

At the same time, I believe that supplements should be chosen and used carefully, since inappropriate supplements or very excessive dosages can potentially be harmful (see below), even though supplements appear to be relatively safe overall and the maximum tolerable dosage for most supplements is quite high. To stay on the safer side, I suggest treating supplements as though they are drugs, not food. Accordingly, it is important to watch for side effects, allergic reactions, adverse interactions (which may be difficult to discern), etc. It may be desirable to start with one supplement, then add one every two or three days, since most adverse reactions usually appear within this time frame. This gives each supplement its own "observation window." Otherwise, if many supplements are given at once and then side effects occur, it will be difficult to determine which one(s) to discontinue. In my mother's case, I did stagger the supplements, but she had no apparent adverse reactions or interactions.

Physicians often advise patients to avoid antioxidants, at least while they are undergoing conventional treatments, because of concern that antioxidants may diminish the effectiveness of radiation and/or chemotherapy. However, this has been a debated issue among informed medical researchers. In my opinion, based on the most recent studies, the current balance of evidence argues against this concern fairly strongly, and even suggests that antioxidants probably enhance the effectiveness of radiation and chemotherapy for most patients, while also reducing their side effects. However, there may certainly be some specific antioxidants which are best avoided, at least while undergoing conventional treatments (see Section 6.5). Many of the references listed in this website provide additional information on this topic, and the following papers provide reviews of relevant studies:
Multiple Dietary Antioxidants Enhance the Efficacy of Standard and Experimental Cancer Therapies and Decrease Their Toxicity, by Kedar Prasad, PhD , Should Patients Undergoing Chemotherapy and Radiotherapy Be Prescribed Antioxidants? by Ralph Moss, PhD , and Antioxidants in Cancer Therapy: Their Actions and Interactions with Oncologic Therapies, by Davis Lamson, ND and Matthew Brignall, ND. Also see the article describing a recently published study by Keith Block, MD and Robert Newman, MD which indicated that use of antioxidants while on chemotherapy is likely to be both safe and beneficial.

A nutritionist who specializes in brain tumors and has advised hundreds of brain tumor patients is Jeanne Wallace, PhD, CNC. She appears to have done a great deal of research, many patients have praised her services, her fee structure is reasonable, and I am comfortable in recommending her. For a video which provides an overview of her approach and recommendations, see Nutritional & Herbal Strategies to Complement Conventional Brain Tumor Treatments (2005). Also see her paper listed in Section 2 of this website, as well as the following somewhat technical document which categorizes ways in which supplements may inhibit tumors: Developing and Monitoring Comprehensive Integrative Nutrition & Botanical Protocols in Cancer Patients. The first page of this document provides statistics which suggest that, overall, Dr. Wallace's patients have historically done considerably better than the norm.

I also recommend considering using the services of the
Centre for Natural Healing headed by Donald Yance, MH, who appears to be a leader in cancer treatment using nutrition, herbs and supplements (see references to his work in Section 2).

I obtain most nutritional supplements from Life Extension Foundation (LEF) (see link in Section 2.1), and some are obtained at a local health food store. Several supplements are also available at major drugstores. For guidance in selecting a reliable supplement supplier, see
Selecting High Quality Dietary Supplements: Finding Companies You Can Trust, by Jeanne Wallace, PhD, CNC.


6.3 Nutritional Supplements Basic List

In my research, I aimed to identify nutritional supplements for which there is good evidence that they are probably effective against GBM and, usually, other gliomas also. Such supplements may also be appropriate for other types of primary brain tumors. The protocol I developed for my mother varied somewhat in terms of specific supplements and dosages, largely because of swallowing issues and complications in scheduling to give her the supplements. However, her basic supplements protocol is described below, and was based mainly on information in the references listed in this website. By spending more time going through this information, I believe the protocol can be improved further, and I'm planning to do that in the future.

- Melatonin at 20 mg/day, taken in one dose right before bed; dosages as low as 5 mg/day are also reported in the literature, and the lower doses may help prevent or reduce daytime sleepiness, but studies showing melatonin to be beneficial for brain tumors and other cancers usually used 20 mg/day; melatonin is readily available, relatively inexpensive, and supported by good evidence

- PSK (polysaccharide K) from Coriolus versicolor mushroom at 3750 mg per day; I haven't come across any reports of side effects from this supplement, regardless of dose; PSK is relatively expensive, but supported by good evidence
Ordering

- Fish oil (EPA and DHA) at 3200 mg/day of these two omega-3 fatty acids, divided into one to three doses per day, taken with food to help prevent upset stomach
Ordering

- Lycopene at 20 mg/day, divided into one to three doses per day, taken with or without food; I haven't run across any reports of side effects from lycopene, regardless of dosage
Ordering

- Genistein and other soy isoflavones at 110 mg/day, divided into one to three doses per day, taken with or without food; some sources suggest much higher doses, but there is conflicting information regarding the suitability of the higher doses
Ordering

- Alfacalcidol (a form of Vitamin D) at 2.4 micrograms/day, based on a
study which used 0.04 mcg/kg/day for glioma patients and showed long-term tumor regression in 2 out of 10 GBM patients (with 5 out of 10 surviving more than 2 years); 1000 to 4000 IU of Vitamin D3 is a viable and much less expensive alternative; monitor blood calcium level if at all possible, since all forms of Vitamin D can raise it and cause a range of side effects Ordering

- Ruta 6C / CalPhos 3X, 9 pills each per day per
Dr. Banerji's schedule ; this supplement is a homeopathic treatment which is inexpensive, quite popular, and there is evidence that some patients benefit significantly, at least for several months, but the percentage of patients deriving such a benefit is entirely unclear to me; the online Ruta groups listed in Section 2.2 are good sources for further information

- Boswellic acid (Boswellin) at 6600 mg/day, divided into three or (preferably) four doses per day, taken with food, preferably fatty food; a more common dose is 1800 to 3600 mg/day, but a maximum dosage of 126 mg/kg/day was indicated in one
study of child and adolescent brain tumor patients; it is important that the dosage be high enough, since a higher dose may provide significant benefit, whereas a smaller dose may provide little or no benefit; most patients take this supplement to control brain edema (See Section 7.1), but it may also provide anti-tumor benefit; it may be preferable to not break open the capsules for this particular supplement; my current opinion is that boswellic acid, when used in higher doses, may be one of the best readily available treatment options for aggressive brain tumors, and personally I would consider a dose of about 8,000 mg/day for an adult, starting soon after diagnosis and continuing without interruption Ordering

- Berberine at 800 mg/day; tastes quite bad if the capsules are opened
Ordering

- Green tea extract (decaffienated) at 700 mg/day, divided into one to three doses per day, taken with or without food
Ordering

- Selenium (as L-selenomethionine) at 400 micrograms/day, divided into one to three doses per day, taken with or without food; avoid doses higher than about 800 micrograms/day since this can result in cumulative toxicity over time

- Bromelain at 3000 mg/day, divided into two or three doses per day, taken without food
Ordering

- Silymarin (30% silibinin) at 900 mg/day, divided into one to three doses per day, taken with or without food


- Quercetin at 1000 mg/day, divided into one to three doses per day, taken with or without food
Ordering

- Artemisinin at 100 to 600 mg/day and artemether at 40 to 80 mg/day, with lower doses preferred for patients in poorer overall health, taken with milk or other fatty food before bed, at least 2 hours after dinner; I've heard that these supplements should not be taken with Vitamin C and iron supplements, and should not be taken until at least 2 months after completing any radiation treatments; possible side effects discussed in the literature include numbness and tingling in the extremeties and hearing loss, but these side effects appear to be associated with much higher doses than described here; there are some anecdotal reports of brain tumor patients seeing benefits within 10 to 14 days, without any side effects, after having failed other treatments and developing recurring tumors
Ordering

Overall, when dealing with a tumor as aggressive as GBM, my current thinking is that it's perhaps best to increase most of these dosages to levels significantly higher than what I've noted above, although this needs to be looked at seperately for each supplement considering it's associated risk of side effects. My rationale is that moderate dosages might slow down tumor growth but still permit growth, whereas higher dosages may stop the tumor growth, or ideally reverse it.


6.4 Other Nutritional Supplements to Consider

There are several supplements which are not currently in my mother's protocol, but which appear worth looking into. They include (in alphabetical order): antineoplastons (very expensive and controversial!), Blood Support , boron, cesium chloride, chlorella, CoQ10, curcumin, DCA (dichloroacetate), D-limonene, DMSO, ellagic acid, Gumbi Gumbi, IP-6 (inositol hexaphosphate), mistletoe (Iscador), resveratrol, methylglyoxal, mushroom extacts other than PSK, Paw Paw, PolyMVA, Protocel, safinur (and oleuropein), samento, shark liver oil (alkylglycerols), thymus extracts, Vitamin A (retinoic acid), Vitamin C (ascorbic acid), and whey protein. I intend to look into them further as time permits.

Currently, the following seem potentially promising to me:

- DCA (as pharmaceutical-grade sodium dichloroacetate), dosed at about 10 to 15 mg/kg/day, possibly in combination with Vitamin C. For more information, see the DCA Site and to order see Buy DCA (but I believe the FDA has recently blocked sale of DCA from this source). A paper published in January 2007 showed DCA to be effective against various cell cultures, including GBM, and also showed substantial shrinkage of tumors implanted in rats within a few weeks. On this basis, I understand that some GBM patients are trying DCA, and I'm aware of one recent report of apparent success in at least temporarily stopping growth of a GBM. I understand that clinical trials may have already started, and the Medicor Cancer Centre in Canada is also offering DCA to its cancer patients, reportedly with "positive response" in 60% to 70% of 35 patients as of September 5, 2007. With respect to side effects, I'm told that DCA may lower blood glucose levels (as in the reported case noted above), may cause peripheral neuropathy in higher doses (which may be reversible), and could potentially also cause dangerous tumor lysis syndrome. DCA is promising, but also carries definite risks, so be careful!

- PolyMVA, dosed at about 2 to 12 teaspoons per day, with 8 teaspoons/day seeming most common. There are several anecdotal reports of success using this treatment, and I'm told that it may take about 3 months for results to become apparent. This supplement is very expensive, but discounts may be available for those who can't afford it.

I've also been told that, in the opinion of one nutritional specialist, artemisinin/artmether should not be taken at the same time as PolyMVA because the two can "cancel out" each other's effectiveness.

If you know of other supplements worthy of consideration by brain tumor patients, please email me at the address in Section 1.


6.5 Supplements and Herbs to Consider Avoiding

As noted above, it is at least possible that some nutritional supplements and herbs may have adverse effects for brain tumor patients. The following are a few that I'm currently aware of for which caution may be warranted:

- St. John's wort (hypericin) may interfere with many chemotherapy drugs (although it may also have anti-tumor effects)

- Yohimbe may interfere with Temodar

- Vitamin C, in high doses, may interfere with Temodar

- Based on test tube studies, curcumin (found in the spice turmeric) may interfere with the chemotherapy drugs CPT-11 (ironotecan), mechlorethamine, and doxorubicin; note that the supplement quercetin is related to curcumin, so the same caution may apply to quercetin (although there is evidence that both curcumin and quercetin also have anti-tumor effects)

- Tangeretin may interfere with Tamoxifen (sometimes used in conjunction with chemotherapy)

- Garlic, gingko biloba, and ginseng may increase the risk of bleeding (although all three may also have anti-tumor effects)

- Ephedra may damage the heart

- Kava may damage the liver

I plan to make this list of supplements as complete as possible, and I request that such supplements be brought to my attention using the email address in Section 1.


6.6 Other CAM Treatments to Avoid

There are also surely a number of other CAM treatments on the market which are either ineffective or even detrimental, and some are also expensive. A further problem is that some patients may rely on such treatments, and thereby forego treatments which may actually be effective. Some of these unsuitable treatments may be well-intentioned, whereas others may be frauds intended to exploit the desperation of cancer patients. Some warning signs to watch out for are:

- Claims which are too good to be true
- Evidence consisting only of testimonials, especially if the sources of the testimonials can't be verified
- Lack of any evidence beyond testimonials
- Evidence reported by questionable sources
- Products with unknown or "secret" composition
- Products with questionable manufacturing quality control
- Sale through multi-level marketing (MLM) programs

None of these warning signs guarantee that a product would not be effective, so investigate a product if it seems promising, but be careful.

I plan to compile a list of CAM treatments which are best avoided by brain tumor patients. I will appreciate any such treatments being brought to my attention using the email address in Section 1.

Quackwatch is a website purporting to identify CAM treatments which are "quack" treatments. However, I've found this website to be nearly useless, due to extreme bias and lack of thoroughness. I would appreciate websites which do an honest and thorough job of identifying quack treatments being brought to my attention.


7. RELATED MEDICAL PROBLEMS

7.1 Decadron (Dexamethosone) and Brain Edema

Decadron is a steroidal drug commonly used to relieve intracranial edema (swelling and pressure in the brain). If uncontrolled, such edema can lead to impaired mental status and weakness, and severe edema can lead to coma or worse.

Decadron is usually effective in controlling edema, however it is associated with the following common side effects, among others:

- Increased appetite, weight gain, fluid retention, puffy face, and heartburn
- Insomnia, depression, nervousness, and mania/mood swings
- High blood sugar, low potassium, high blood pressure, and increased risk of infection
- Thinning hair, rash or acne, thin skin, and facial hair growth
- Muscle weakness, osteoporosis, and cataracts

Because of these side effects, it is desirable to keep the dosage of Decadron as low as possible, while still adequately controlling edema. When reducing Decadron dosage, it is extremely important that the dosage be "tapered" gradually under physician supervision, since abrupt reduction in dosage can cause very serious adverse consequences. For guidance on tapering, see
Dexamethasone Therapy in Patients with Brain Tumors - A Focus on Tapering.

The drug Xerecept is in clinical trials and offers the potential to control edema with less side effects than Decadron. The anti-angiogenic drug AZD2171 (also known as Recentin and cediranib) is also in clinical trials and offers the potential to both reduce edema and control GBM growth.

The nutritional supplements boswellic acid and bromelain (see above) are also commonly used by brain tumor patients to help control edema, and boswellic acid appears particularly effective for this purpose. I have not found any information which suggests that they should not be used in conjunction with Decadron, and many patients have followed this approach without any evident adverse interactions.

For a list of various options to consider (not all of which I've reviewed), see
Brain Edema Options.

For details on the mechanisms of brain edema, see
Mechanisms of Tumor-Related Brain Edema, by Walter Strummer, MD.

For cautionary comments regarding use of Decadron at the same time as the anti-seizure medication Dilantin (phenytoin), see
Dexamethasone/phenytoin interactions: neurooncological concerns.


7.2 Seizures

Seizures are a common problem among brain tumor patients, and therefore further information on this topic is forthcoming.

For cautionary comments regarding use of Decadron at the same time as the anti-seizure medication Dilantin (phenytoin), see Section 7.1 above.


7.3 Infections

Infections are a common problem among brain tumor patients, and therefore further information on this topic is forthcoming.


7.4 Pain

Information on this topic is forthcoming.


7.5 Other Medical Problems

Patients may experience a variety of other medical problems. Some of these may be related to health conditions which existed prior to the tumor diagnosis, and some may be side effects of treatment. Management of side effects will be discussed to some extent in other appropriate sections of this website.

Other medical problems must be addressed on an individual case by case basis, so I recommend that you promptly bring such problems to the attention of your physician. If your physician does not appear to take a problem seriously enough, or if your problem is being passed from one physician to another without resolution, insist that one qualified physician take full responsibility for resolving the problem.