Transcript of Live Chat, from June 4, 2000
Guest Host: Dr. Henry Friedman, Neuro-oncologist from Duke University Medical Center.
Moderator: Al Musella, DPM President, Musella Foundation Location: Virtualtrials.com Auditorium

[musella] What do you see as the most promising treatment in the future for gbm?

[DrFriedman] there is no one most promising rx---many different strategies will contribute--ijc. vaccines, gene therapy, reversal of drug resistance to name just 3-all of them will help to chip away at the problem

[musella] #2: a related question: Do you think it is better to mix up chemo`s so the diffuse pontine glioma tumor does not develop a resistence a specific chemo, or stay on temador if the patient is responding well? What do you think combining thalidomide with temador? I read that it could possibly compromise the effectiveness of temador.

[DrFriedman] in general, if you are dealing with a newly dx tumor, switching to alternate drugs is a sound approach to avoid the development of resistance. if howeve, you are treating a recurrent tumor, which has clearly responded to a specific therapy, staying with that therapy makes sense. it is too early to understand what, if anything thalidomide does--however, it is not likely to compromise therapy given with it.

[musella] Tab asks: If you`re familiar with SU5416, would you explain how it is supposed to work in layman`s terms?

[DrFriedman] su5416-- I believe it is an anti-angiogenesis agent but have not used it and will need to check further re: its mechananism of action. there is laba data but no clinical data supporting its benefit yet for patients.

[musella] tab also asks the same question with 06-bg and/or Patrin 2 (An oral drug - similiar to 06-bg) these agents deplete agt, or 06-alkylguanine-dna alkyltransferase, which is an enzyme that is the major mechanism of resistance to nitrosoureas such as bcnu and to methylators such as temodar.
[musella] Any early results yet on if they work? or have any major side effects?

[DrFriedman] they are very successful in the animal models of human tumors and also effective in depleting agt in tumors in patients. we will know within the next year if they can restore sensitivity to chemotherapeutic agents in patients

[musella] What do you think of the dendritic cell immunotherapy trials they`re doing at Cedars Sinai?

[DrFriedman] I believe that the use of dendritic cells to presnet antigens to a persons own white cells as a means of generating an immune response is scientifically sound. however, to do the trials in a sophisticated fashion, you have to have a means of measuring in the lab the development of the immune reaction. also, you should be targetting a specific antigen on the tumor that is not expressed on normal brain or other tissues. neither of the

[musella]popis asks: I have a cavernous sinus meningioma and want to know what treatment is best for these tumors: Gamma Knife or FSR (fractionated stereotactic radiosurgery)? Also - is RU-486 of any use with these tumors?

[DrFriedman] this is difficult to answer without seeing the mri---it is possible to one of several differnet strategies to treat this tumor. ru-486 is a progesterone antagonist which is possible helpful if the tumor has progesterone receptors.

[musella] Dune asks:have you ever seen a long term survivor of a pediatric diffuse brainstem glioma?

[DrFriedman] there are a few such survivors I am aware of---however, these were in general young children who may have had a biologically different tumor.n

[musella] A follow-up question from Dune: What are the options, and what is your treatment of choice for a pediatric diffuse intrinsic pontine glioma that had a 95% reduction in tumor from stereotactic radiation with concurrent daily temador ? I do not want to wait until the tumor grows back and then do something.

[DrFriedman] I couldn't agree more-- I would favor an adjuvant chemo program that would include temodar but other agents as well--perhaps bcnu with cpt-11----building on the adult malignant glioma data.

[musella] susan asks: What is your opinion about Dr. Burzynski`s treatment in Texas? Is there any validity to his treatment? How do you feel about the rights of a parent to decide what treatments a child gets, vs. the FDA deciding?

[DrFriedman] I am on the public record as stating that although I have seen no data that proves that antineoplastons do not work, I have also, nor has anyone else, seen data that proves they do work. I remain sceptical of any benefit from their use. I believe that if a therapy of known benefit has a high liklihood of helping a child, a parent does not have the legal right to deny the child that therapy. if the therapy has a poor chance, then

[musella] niels2 asks: Is necrosis a definitive sign of glioblastoma? What consequenses does the percent of necosis in the tumor have for the prognosis?

[DrFriedman] necrosis occurs when something dies--this can result from successful therapy or the rapid growth of a tumor such as a gbm growing faster than its blood supply can meet the needs of the tumor, which then develops necrosis. I know of no correlation between the degree of necrosis and biological behavior of the tumor.

[musella] Day asks: We`ve recently seen a drug called C225 in the news? What is your assessment of it for GBM? Also same question for a drug called: mommastantin

[DrFriedman] c225 is an epidermal growth factor receptor antagonist, a class of drugs which may prove helpful in the rx of gbm---several programs, inc. ours at duke, wil soon begin evaluating another such compound--zd 1839. I am unaware of the other agent

[musella] tab asks: Did you release the results preliminary from Temodar/CPT-11/BCNU rotation protocol yet?

[DrFriedman] this is not a protocol--we are treating patients after surgery nad rt, who are not eligible for a trial, with this rx because we feel it is the best available option. however, as our trials mature, we change this best available rx accordingly. the fact that we have a cohort of patients with gbm who remain progression free 2-4 years from dx is heartening but we do not have the data, sice we change the rx ove time, to really know

[musella] tab also asks: What`s the best test for distinguishing tumor from necrosis? PET, SPECT, MRSpectroscopy, MRI,etc?

[DrFriedman] there is no best test--all of them have inherent flaws---the only reliable test is a biopsy

[musella] FrankMartens asks: Would Tamoxifen be a wize choice if AAIII patient has really low Nutirfil counts and has to wait a long time before the nect CCNU dose? [musella] I add: does tamoxifen have a place in the treatment of glioblastomas?

[DrFriedman] absolutely as long as they do not have history of a blood clot.

[musella] paultlaf asks a related question: Dr Friedman: What are your thoughts on augmenting Temodar with high dose Tamoxifen ?

[DrFriedman] no problem with this-- we have done it a duke for certain patients.

[musella] frances asks: Dr. Friedman,I have seen alot of articles about a new drug il-4,will Duke have trials using this drug for glioblastoma. Thank you Frances

[DrFriedman] no--we believe the data for this is not very sound and that at least some trials with it have been put on hold

[musella] Paul asks: from what area of BT therapy, ie: gene therapy, immunotherapy. anti-angiogenesis, etc.. do you think that the cure will eventually come? and how long before we see true progress

[DrFriedman] absolutely but no one therapy will do it---a patient with a gbm should take advantage of those approaches which hold promise and know that the longer they live the more options will become available. this is a tumor which will someday, hopefully in he next number of years, have much more effective rx available.

[musella] Anonymous asks: Do you ever recommend any alternative treatments for pediatric diffuse pontine glioma? In conjunction with standard treatments, or alone?

[DrFriedman] I believe that if a family wants to use an alternative agent along with more mainstream rx, that is fine as long as there are no major toxcities likely to be seen---people for example have died from laetrile.

[musella] Manuel asks: Is Temodal `the best` treatment to GBM? If not what is? For a 4 year old newly diagnosed - what would your prefferred treatment plan be? - My son was four yo when dx, last december. We were told that if he was younger than 4 or older than 7, his chances could be higer. When he reaches 7 years of age, does it mean he will have better chances?

[DrFriedman] I do not know why the ages were quoted--they have little relevance. there is no best therapy---surgery to resect as much as possible, followed by a program of rt and some chemo using the newer options makes the most sense.

[musella] tab asks: What`s your recommendation for a patient who has been on Temodar for 6 months and then has a recurrence? What are the next options?

[DrFriedman] if this is a gbm, then it depends on the mri and the patients clinical status. there are many options and without seeing the mri it is hard to give a specific rec. however, we would be pleased to review the scan etc at duke and try to help. we do this frequently

[musella] nancy asks: My father died of a gbm last year. His neurosurgeon never mentioned participating in clinical trials and `poo-pooed` our suggestion that it might be a treatment option. Only at our insistence, did his participation take place. I`ve spoken to so many other brain tumor and other cancer patients that have had similar experiences. This participation is so important to the development of new, more effective treatments. My question is this...what is you thoughts on WHY this occursm and what can be done to reverse it?

[DrFriedman] the single most challenging problem is the nihilism which most physicians have--they believe a patient wiht a gbm is dead. only with the use of the newer more scientific approaches will there be progress. we have too many survivors to ever adopt this give up before you start the fight philosophy

[musella] Connie asks: My husband (age 52)was diagnosed with gbm 10-1-99, junction of frontal & parietal lobes, gliadel wafers inserted during 95% resection, 7 wks radiation, 2 new tumors found & included in radiation boost, now in 7th round of Temodar/Accutane (cis-retinoic acid), no change in first 3 tumors, but now there is a new 4th one - too deep for surgery. Do you have any suggestions on our next step? [musella] Musella adds: what are you thoughts on combining cis-retinoic acid with temodar 9and maybe tamoxifen)?

[DrFriedman] again, specific patient questions can best be answereed if I have scans to review.

[musella] chuckn asks: Dr. Friedman, thanks for taking the time to be with us. I believe you see about 700 new cases per year? Generally what is the composition of these? Do you see an increase/decrease in certain tumor types?

[DrFriedman] I see about 100 kids and 600 adults new to duke each year--there are about 400 of these adults with gbm.

[musella] nick asks: what are you thoughts on the gliadel wafers? Any better results in the trials for the higher dose versions?

[DrFriedman] gliadel wafers are a reasonable attempt to help with the control of the primary site--too soon to say if the higher doeses will add more control at this site.

[musella] howardcrystal asks: What do you think of the very good European results from the abstract posted at ASCO about Temodar dosing for 21 days on seven off, rather than five day dosing.

[DrFriedman] too son to say---we know that temodar is a good drug--we do not yet know the best regimen.

[musella] We have a few more questions on temodar: [musella] Does it interfere with anti-seizure medications?

[DrFriedman] not to my knowldege

[musella] Does it have to be taken on an empty stomach? [musella] How long can a person stay on it if they are doing well?

[DrFriedman] yes--preferably 1-2 hours after the last meal--however, this may be a over cautious step since food does not apear to alter the absorption.

[musella] Day asks: Do you anticipate your research team at Duke conducting any clinical trials utilizing angiostatin or endostatin? What has stopped some of the trials involving these drugs?

[DrFriedman] we will be conducting a series of trials using anti-angiogenesis agents--not sure what is the problem with the 2 you mentioned--possibly availability due to difficulties in making them. we will use perfusion mri to try and actually see what the drugs are doing.

[musella] Henry asks: what options are there for breast metastases to the brain?

[DrFriedman] rt remains the mainstay but several programs, inc. duke, are evaluatijg the role of drugs like temodar or cpt-11 to provide help.

[musella] JohnR asks: What is you opinion of the `watch and wait` strategy? Does it make a difference to your answer whether someone has had a complete response (no radiologically detectable tumor) to conventional therapy or just a stable tumor?

[DrFriedman] if you are talking aabout a gbm, that is like asking what do you prefer--an oil change or a new engine/car. I believe that there are options out there, like temodar, ccnu, cpt-11 etc. which can be used without cheapening the quality of like of the patient and which may delay or even prevent tumor growth. I do not wait for the tumor to recur before offering these treatments.

[musella] dune asks: I heard that in a period of time that over 80% of resected brain tumors had monkey virus in them from polio vaccines, do you think there is any correspondence with any vaccinations and pediatric brain tumors?

[DrFriedman] unknown---of interest but never proven to have a relationship.

[musella] tab asks a similiar question, to clarigy: For gbm, after surgery and radiation, do you think wait-and-see is ok or should you use chemo before any recurrence?

[DrFriedman] use chemo etc.

[musella] aim asks: How do you get in a trial? [musella] and how do you pick one?

[DrFriedman] check with the major institutions asking questions for patients with brain tumors---duke, md anderson, ucsf, etc. also, you can call in the us 1 800 4 cancer, which is the hotline of the national cancer center. of course, als web site (ed. Note: virtualtrials.com) may be the best centralized source of clinical trial data.

[musella] Jan asks: jan what chemical agents do you consider hopeful for the treatment of benign meningiomas? which are available now?

[DrFriedman] hydroxyurea, interferon, and maybe ru-486.

[musella] Bud asks: What do you think of Thalitamide(?) as a preventative after AAIII surgery and rt? Also - what ever happened with poly ICLC? We used to hear a lot about it?

[DrFriedman] thalidomide was evaluated in a worst case scenario--patients with bulk recurrent disease--not a good place to se if an anti-angiogenesis drug will work. too soon to know what it will add. poly iclc was never that promising and remains in the same place--no news of any true benefit

[musella] Ann: Is there any proof that treatment at a major brain tumor center results in better outcomes than a local hospital (for a gbm)?

[DrFriedman] I have seen data to that effect in the journal of the national cancer institute. certainly, I believe that that is where progress will be made--no way to say in any specific patient that it will increase survival. however, you know what happens with surgery, rt and bcnu--the community standard---why settle for that if there is a chance of doing better at a center that focuses on brain tumors.

[musella] Chris asks: Are there chemotherapies which have been proven effective against juvenile pilocytic astrocytoma in children?

[DrFriedman] carboplatin alone or with vincristine, vp-16, cyclophosphamide.

[musella] JohnR To clarify my question re `wait and see`. I have had rad and CCNU. No detectable tumor for last 20 months. Originally dx`d gbm. Pathology recently recently re-evaluated as tentative gbm...not enough biopsy material to rule out large oligo or low grade astro components.

[DrFriedman] the path should be reviewed at a center--that will be critical to give you an answer

[musella] chuckn asks:Dr. Friedman. Many of our cases unfortuneatly progress into serious stages. At the time `agressive` treatment seems called for. I`ve seen those described as blood brain barrier disruption, intra arterial chemo. In this category what are the treatments you find more effective? Is stem cell treatment among these?

[DrFriedman] none of the above have any proven track record. aggressive does not mean better---a more logical approach would be to use a more scientifically supported approach.

[musella] is 06-bg available, to be given with temodar, off trial (compassionate use)?. Do you give it to any of your patients on temodar yet? How did they do?

[DrFriedman] I have used temodar for the past 5 years with success in many setting. the trial of o6bg plus temodar, for patients who have failed temodar, will start in the next 4-6 weeks.

[musella] Pete: How do I go about `sending you slides`, do I request an authorization from my insurance for a 2nd (actually 3rd) opinion and rhen have MGH forward them to you?

[DrFriedman] yes.

[musella] Do you ever recommend vegitarian diets or life style changes?

[DrFriedman] vegetarian diets, if that is yor pleasure, are fine as long as you supplement with the appropriate minerals and vitamins. I do not recommend this diet just to fight the tumor. depends what your life style was to begin with--you need to remain positive and take advantage of the newer options.

[musella] We only have 2 minutes left.. I want to ask my own general questions: If a patient presents to you with a newly diagnosed GBM, what would your best treatment plan consist of?

[DrFriedman] depends on the clinical status of the patient and the post surgical mri--we might offer further surgery, monoclonal antibody, pre-rt chemo, or go right to rt and then build on that.

[musella] And lastly: how is your trial of monoclonal antibodies going?

[DrFriedman] the overall median survival to date for newly dx patients in 90 weeks--which means we have a lot of patients who are 2-4 years out and progression free. moreover, the newer antibodies that are truly tumor specific, are soon going to be used by us.

[musella] Thank You Dr. Friedman!

[DrFriedman] my pleasure--thanks for the opportunity to do this.