Monday, October 6, 2014

Memantine and WBRT

After the whole brain radiation review that my collaborators and I just published came out, my friend and colleague, Jack West, put a nice post up on his website Cancer Grace about it and asked a follow up question on twitter:

He was referring to the recent Radiation Therapy Oncology Group's trial of memantine (a drug for dementia) given during whole brain radiation: RTOG0614.  So, to answer, I polled a couple of my friends who do nothing but neuro-oncology and reread the results of the trial (not out in published form yet, just as an abstract (paper #1 on this page) and the full talk from ASTRO).

As a quick summary: Whole brain radiation therapy (WBRT) is a treatment given to patients who have metastatic cancer in their brains.  There are a number of situations in which WBRT is given and it improves survival and significantly improves the life of patients.  On the downside, it has been shown to cause cognitive decline with as many as 60% of patients exhibiting measurable decline at 4 months after WBRT.  So, to combat this, a trial of memantine during and immediately after WBRT, an NMDA-receptor blocker used to treat Alzheimer's dementia was proposed and carried out.

In this trial, about 500 patients were enrolled, stratified by their RTOG brain metastasis RPA class (they only enrolled class 1 and 2 patients) and given either 20mg of memantine or placebo daily for 24 weeks.  A lot of their patients weren't able to be properly analyzed because of issues with survival (sadly, to be expected in this population), but those who were evaluable (~150) took a battery of 6 different cognitive tests.  The primary endpoint was performance on a specific test at the 24 week point, the e Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) and there was NOT a significant difference in the results of this (but it 'teetered on the edge of significance', with a p-value of 0.059).  Now, don't get me started on p-values.  Oops, too late.

The all holy p<0.05 is an arbitrary cutoff level by which we determine 'significance'.  I say again, arbitrary.  What it has become, I fear, is a gold-standard for a 'positive study'.  So in the case of this one, which technically did not meet its primary end point, many people are not swayed, because p wasn't less than or equal to 0.05.  the secondary endpoint, cognitive decline (a measure using several other of the tests) was met with p=0.01 and, crucially, there were no difference in side effects or survival. My *suspicion* is that the primary endpoint will be met if they can accrue (and analyze) another 50 patients, and this debate will end. However, until then, the jury is out.

Personally though, even though it failed to meet its primary end point, I will be recommending memantine to patients in a favorable RPA class getting WBRT, or at the very least having this discussion with my patient.

As an aside, the two Neuro specialists I polled had opposite answers, so it is fair to say that this remains in the undetermined category. But, the drug has been shown to be safe, and now *likely* efficacious. In a situation where we don't have other options, I'm sold.

14 comments:

  1. I was in trouble when my doctor told me that i have been diagnosed with
    HIV DISEASE and i know my family will face a serious problem when i am gone, i
    lost hope and wept most of the time, one peaceful day i look at the internet and
    i saw Dr. OYAKHIRE testimonies and i followed him up in a GOOD WAY. I called him and he
    guided me through out everything. i asked him for solutions and he started the remedy for my
    health, thank God, now everything is fine and i am cured of my HIV by Dr ihibor herbal
    medicine, am very thankful to Dr.OYAKHIRE , contact him today 0n whatsapp +2347084100646 and be free from your Diseases / Virus / Infection // because he is very good and honest Doctor. contact him via email; droyakhireherbalhome@gmail.com / mobile whats-app +2347084100646....One thing i love most about Dr. OYAKHIRE is honestly and he is very polite with his patience, so everything he told me was what he did, and his herbal medicine are very affordable to get, Dr OYAKHIRE god will over bless you.
    He can as well cure the following diseases;

    Herpes,
    Asthma,
    Cancer,
    HSV1, &
    HSV2,
    Hepatitis B,
    HIV/AID ETC.

    ReplyDelete
    Replies





    1. Hi Friends i am so glad to writing this article today to tell the world how Dr Sayo cured my HSV VIRUS,i have been detected with HSV-1 AND HSV-2 since five years ago, ever since then my life has been in complete bizarre and agony,i have used so many drugs that was prescribed to me by several doctors,but it didn't cure my HSV VIRUS neither did it reduce the pain,until a certain i was checking for solution in the internet,then miraculously came across Dr Sayo the powerful herbalist that cure numerous individuals HSV-1 AND HSV-2 INFECTION,then i contacted his email: sayoherbalhealer@gmail.com i explained everything to him and prepared a cure that cure my HSV-1 AND HSV-2 disease totally after receiving his herbal medicine, so my friends viewers why wait and be suffer when there is someone like Dr Sayo that can cure any disease HIV/ CANCER/ HEPATITIS B VIRUS, you can contact his via email: (sayoherbalhealer@gmail.com) check his FB page:  https://www.facebook.com/Sayo-Herbal-Healer-100145798345000/ OR visit his websites website; http://sayoherbalhealer.website2.me/  check blog: https://sayoherbalhealer.blogspot.com/  






















      Hi Friends i am so glad to writing this article today to tell the world how Dr Sayo cured my HSV VIRUS,i have been detected with HSV-1 AND HSV-2 since five years ago, ever since then my life has been in complete bizarre and agony,i have used so many drugs that was prescribed to me by several doctors,but it didn't cure my HSV VIRUS neither did it reduce the pain,until a certain i was checking for solution in the internet,then miraculously came across Dr Sayo the powerful herbalist that cure numerous individuals HSV-1 AND HSV-2 INFECTION,then i contacted his email: sayoherbalhealer@gmail.com i explained everything to him and prepared a cure that cure my HSV-1 AND HSV-2 disease totally after receiving his herbal medicine, so my friends viewers why wait and be suffer when there is someone like Dr Sayo that can cure any disease HIV/ CANCER/ HEPATITIS B VIRUS, you can contact his via email: (sayoherbalhealer@gmail.com) check his FB page:  https://www.facebook.com/Sayo-Herbal-Healer-100145798345000/ OR visit his websites website; http://sayoherbalhealer.website2.me/  check blog: https://sayoherbalhealer.blogspot.com/  




      Delete
    2. I was cured of CANCER with the used of natural herbs. My name is Mella Ken and am from US. I love herbs so much. Most times, injection and drugs are just a waste of time. I was cured 8 months ago, i suffered from CANCER for 3 yrs but with the help of Dr.Sayo herbal medicine, i was cured within few weeks of drinking the herbs he sent to me through courier delivery service. This same doctor also cured my Aunty from FIBROID, as soon as i heard she had FIBROID, i quickly refer her to Dr.Sayo and she was cured too after drinking his herbs.I have referred more than 15 persons to Dr.Sayo and they were all cured from their various illness. Have you taken herbs before?. You have spent so much money on drugs,injections,surgeries etc and yet you have no good result to show for it. Contact Dr. Sayo now, he is a herbalist doctor, i assured you of a cure if you drink his natural herbs. Dr.Sayo have herbs that cures Hiv, Herpes, diabetics, asthma, hepatitis, HBP, STD, cancer, chronic, etc. Contact Dr Sayo through his Email address on: sayoherbalhealer@gmail.com or WHATSAPP/CALL him on+2349012175679 Visit his FB page: https://www.facebook.com/Sayo-Herbal-Healer-100145798345000/    
      also visit website: http://sayoherbalhealinghome.com/ or check blogs: https://naturerootandherbscures.blogspot.com/ Please share the good news to other people once you are cured    

      Delete
    3. Life has not been easy for me, I am here to share the good news of my life, how I was cure through HSV2 by doc Aziegbe who help me within 2 weeks with the help of his herbal medicine I am from United states of America, so this Great doctor sent me a herbal which I took according to the way he instructed, just to find out I am cure after taking the cure for 2 week I found this man email from the internet, how he also help a lady from the same sickness. I am so happy to be writing this testimony to the world because this man really clean the tears in my heart and he is a man of his words I want to use this means to inform those of us who’s doctor had told there is no cure, well here is the chance to get yourself cured from this horrible sickness you can get Dr Aziegbe email here DRAZIEGBE1SPELLHOME@GMAIL. COM or you can also whatsApp him +2349035465208 and the doctor also told me he can fix this sickness also: 1. HIV / AIDS 2. HPV 3. CANCER 4. ALS (Lou Gehrig’s disease) 5. Hepatitis B

      Delete
  2. HOW I WAS ABLE TO FLUSH OUT THE HERPES VIRUS WITH THE HELP OF DR. KHAM NATURAL PRODUCT, HIS EMAIL dr.khamcaregiver@gmail.com. I was diagnosed with Herpes a year ago. It’s the worst thing that’s ever happened to me and  I feel like my life is over. Living with constant pain is something no one should have to go through, Herpes has also had a huge impact on my sleep . Since being diagnosed I’ve fallen so far into depression I see no way out because i have been to different hospital. I’m taking a high dose of antidepressants, as well as sedatives and sleeping-pills. I don’t know how I’ll ever accept that this is my life now…I keep asking why me because know changes? But I guess reading your testimony really made me feel happy because i believe what i had from people out there who you also help to cure the herpes virus, and i believe so much with your herbal medicine i am going to be out of this bad situation like others you also help before, what we i have done if not for the herbal medicine that i requested for that was able to flush out the bad virus that was making me go crazy. people out there how will i thank this man called DR. KHAM, i will advice you to email him direct if you have disease like herpes etc. dr.khamcaregiver@gmail.com or whatsapp him +2348159922297

    ReplyDelete
  3. Hi Friends i am so glad to writing this article today to tell the world how Dr Sayo cured my HSV VIRUS,i have been detected with HSV-1 AND HSV-2 since five years ago, ever since then my life has been in complete bizarre and agony,i have used so many drugs that was prescribed to me by several doctors,but it didn't cure my HSV VIRUS neither did it reduce the pain,until a certain i was checking for solution in the internet,then miraculously came across Dr Sayo the powerful herbalist that cure numerous individuals HSV-1 AND HSV-2 INFECTION,then i contacted his email: sayoherbalhealer@gmail.com i explained everything to him and prepared a cure that cure my HSV-1 AND HSV-2 disease totally after receiving his herbal medicine, so my friends viewers why wait and be suffer when there is someone like Dr Sayo that can cure any disease HIV/ CANCER/ HEPATITIS B VIRUS, you can contact his via email: (sayoherbalhealer@gmail.com) check his FB page:  https://www.facebook.com/Sayo-Herbal-Healer-100145798345000/ OR visit his websites website; http://sayoherbalhealer.website2.me/  check blog: https://sayoherbalhealer.blogspot.com/  

    ReplyDelete
  4. I was cured of CANCER with the used of natural herbs. My name is Mella Ken and am from US. I love herbs so much. Most times, injection and drugs are just a waste of time. I was cured 8 months ago, i suffered from CANCER for 3 yrs but with the help of Dr.Sayo herbal medicine, i was cured within few weeks of drinking the herbs he sent to me through courier delivery service. This same doctor also cured my Aunty from FIBROID, as soon as i heard she had FIBROID, i quickly refer her to Dr.Sayo and she was cured too after drinking his herbs.I have referred more than 15 persons to Dr.Sayo and they were all cured from their various illness. Have you taken herbs before?. You have spent so much money on drugs,injections,surgeries etc and yet you have no good result to show for it. Contact Dr. Sayo now, he is a herbalist doctor, i assured you of a cure if you drink his natural herbs. Dr.Sayo have herbs that cures Hiv, Herpes, diabetics, asthma, hepatitis, HBP, STD, cancer, chronic, etc. Contact Dr Sayo through his Email address on: sayoherbalhealer@gmail.com or WHATSAPP/CALL him on+2349012175679 Visit his FB page: https://www.facebook.com/Sayo-Herbal-Healer-100145798345000/    
    also visit website: http://sayoherbalhealinghome.com/ or check blogs: https://naturerootandherbscures.blogspot.com/ Please share the good news to other people once you are cured    

    ReplyDelete
  5. Life has not been easy for me, I am here to share the good news of my life, how I was cure through HSV2 by doc Aziegbe who help me within 2 weeks with the help of his herbal medicine I am from United states of America, so this Great doctor sent me a herbal which I took according to the way he instructed, just to find out I am cure after taking the cure for 2 week I found this man email from the internet, how he also help a lady from the same sickness. I am so happy to be writing this testimony to the world because this man really clean the tears in my heart and he is a man of his words I want to use this means to inform those of us who’s doctor had told there is no cure, well here is the chance to get yourself cured from this horrible sickness you can get Dr Aziegbe email here DRAZIEGBE1SPELLHOME@GMAIL. COM or you can also whatsApp him +2349035465208 and the doctor also told me he can fix this sickness also: 1. HIV / AIDS 2. HPV 3. CANCER 4. ALS (Lou Gehrig’s disease) 5. Hepatitis B

    ReplyDelete
  6. Before people said there is no cure for herpes virus but today many people have now believe that there is a cure,herpes virus can be cured through Africans roots and herbs, Dr.chala he is the one of the great herbal doctor in Africa and he has the cure on this virus last month he share his herbal medicine in some medical hospital and now he is well recognize as one of the best in Africa, you don’t have to be sad any more or share your tears any more on this virus when the cure have already be find by Dr.Chala email him on dr.chalaherbalhome@gmail.com or https://
    drchalaherbalhome.godaddysites.com or https://mywa.link/dr.chalaherbalhome

    ReplyDelete
  7. HERBAL DR EMU WHO PREPARE HERBAL MEDICINE TO CURE ALL KINDS OF DISEASES INCLUDING HERPES DISEASE.   
     I have been battling this Herpes disease for almost 3 years now....I tried all possible means to get cure from my Herpes Disease but all to be in vain until i saw a post in a health forum about a herbal Dr Emu who prepare herbal medicine to cure all kind of diseases including Herpes Disease, at first i doubted if it was real but decided to give it a try...when i contact Dr Emu via his email (emutemple@gmail.com)  write him and reply me explain how the process work so after ordering for the medicine I got it within 3/4 working days through DHL Delivery and I took it according to the way Dr Emu instructed, I was so happy after 2 week I took the medicine there was very big change in my health when I was done with the process I go for test, I found out I am negative...Herpes patients should also get in touch with this herbalist Dr Emu to get rid of these Herpes Virus forever his whatsapp number +2347012841542. Website: https://emutemple.wordpress.com/ 

    ReplyDelete
  8. Happiness is all I see now I never thought that I will be cured from HERPES virus again. I have been suffering from a deadly disease (HERPES) for the past 4 years now, I have spent a lot of money going from one place to another, from church to church, hospitals have been my home every day. Constant checks up have been my hobby not until this fateful day, I was searching through the internet, I saw a testimony on how DR Omongbe helped someone in curing his HERPES disease, quickly I copied his email which is dromongbenaturalremedies@gmail.com just to give him a test I spoke to him, he asked me to do some certain things which I did, he told me that he is going to provide the herbal cure to me, which he did, then he asked me to go for medical checkup after some days after using the herbal cure, behold I was free from the deadly disease, he only asked me to post the testimony through the whole world, faithfully am doing it now, please brothers and sisters, he is great, I owe him in return. if you are having a similar problem just email him on ( dromongbenaturalremedies@gmail.com ) or you can whatsApp his mobile number on +2348050407265 Visit his website https://dromongbenaturalre.wixsite.com/dromongbenaturalreme

    ReplyDelete
  9. I have been a herpes carrier for 2 years and I tried every possible means
    of curing but all of no useful until I saw a health promotion on a
    herbalist from Africa who prepares herbal medicines to cure all sorts of
    diseases including cancer and many others sickness, I first doubted It was
    not true but decided to try, when I contacted this herbal physician via his
    email, I purchased herpes herbal medicine and received it within 7 days
    and used it as prescribed, I tested negative within 3 weeks of use, do not
    lose hope to contact him early If you need help, am convinced he can help you too,
    He is also special in curing 1.
    HIV/AIDS 2. HERPES 3. CANCER 4. ALS 5. HEPATITIS B 6. DIABETES 7. HUMAN
    PAPILLOMAVIRUS DISEASE(HPV) 8. ALZHEIMER 9. LUPUS (Lupus Vulgaris or Lupus Eratosthenes)ETC,,,,,, You can also visit his website:
    http://drchalaherbalhome.godaddysites.com
     email him on dr.chalaherbalhome@gmail.com

    ReplyDelete
  10. Hello Am From The UK , I want to write a little testimony about the good work of doctor Oyagu who cured me from Hsv 1 and 2 for just 2 weeks with his herbal medicine, I never believe I can be normal again and have a good life like others I always regretted the day I got diagnose with the virus, I was lost of hope when my doctor told me there is no cure for it but I keep thinking and thinking about my future, if I can have kids of my own well I am so grateful for my helper who get me cured with his herbal medicine, I go online in search of anything that can help me because I can’t deal with it forever so I found this doc Oyagu email on a blog of someone who was cured by him I quickly contact him for help and explain all my pain to him, he told me not to worry about it there is cure for real, I never believe until he send me the herbal medicine when I order for it and I have it within 4 days that is how I took the medicine for 2 week and the following week I go for test just to confirm I was 100% cured from this sickness what a miracle in my life I am so happy right now, you can also get in contact with him if you have such sickness through email address oyaguherbalhome@gmail.com or text him on what's app, phone number +2348101755322 or visit his website https://oyaguspellcaster.wixsite.com/oyaguherbalhome Dr Oyagu also has remedy to others disease like COLD SORES,HIV/AIDS,DIABETES.CANCER,HIGH BLOOD PRESSURE AND MANY MORE. I oblige everyone to contact this powerful herbalist Dr Oyagu and be free from suffering.

    ReplyDelete
  11. To know more about Chief Dr Lucky you can visit his website (https://chiefdrluckyherbaltherapy.wordpress.com/)
     
     A friend that suffered from Herpes and was cure with the help of this great herbal doctor Chief Lucky so i decided to contact him for help in getting rid of my families genital herpes virus 1/2 which i did and all i was told to provide was just some useful information and some materials used in preparation of the natural cure and that i did and now i am the happiest person on earth because i am writing this testimony of mine with joy and happiness in my heart to the whole world to know that natural remedy is real because i am a living testimony of Chief Lucky traditional herbal cure and i want you all to contact Chief Lucky via his email: chiefdrlucky@gmail.com or WhatsApp him +2348132777335 am sure he will help you too.

    ReplyDelete