Sertraline vs Fluoxetine

Steven and others…

I have been considering switching from Sertraline to Prozac.  I would appreciate your thoughts:   

Heres what I know based on what Steven has written on his web site.

·           

• When sertraline was added to doxorubicin it resulted in increased chemosensitive over fluoxetine and doxorubicin.  This is apparently due to sertraline’s ability to impact efflux pumps better than fluoxetine.  I do not know if TMZ and doxorubicin are comparable with regards to benefits brought about by inhibiting efflux pumps.

•    Prozac inhibits MGMT activity, sertraline does not

•     Disulfiram inhibits MGMT activity

Then from CUSP9*:

•  Sertraline blocks multiple survival pathways.  No mention of this is made with fluoxetine

So here are my questions:

• If sertraline inhibits efflux pumps as does disulfiram, how important are PPI’s likely to be if both sertraline and disulfiram are already being utilized?

• Since disulfiram already inhibits MGMT activity, in theory fluoxetine would not need to be used for this (ignoring the possibility of synergy for now).  And since both sertraline and fluoxetine inhibit efflux pumps, it seems sertraline might be better combined with disulfiram rather than fluoxetine and disulfiram because sertraline has the added benefit of blocking multiple survival pathways.  Do you agree with my thinking on this?

• Fluoxetine does inhibit MGMT as does disulfiram and I suspect the synergy between the two could be beneficial, but since we are dealing with an IDH1 mutation, presumably most of the cells are MGMT methylated.  There would of course be other cells that are not methylated that could benefit from MGMT inhibition, but with disulfiram in the mix already, do I need to prioritize fluoxetine over sertraline because of this?  Or would the added benefit of blocking survival pathways be of more importance?  I realize there is no known answer to this and I am asking you to offer input lacking any data, but I am wondering if based on what you have read, this makes sense.

• Jeremy is not willing to add a PDE5 inhibitor to his cocktail.  I think he has had his fill of drugs and supplements.  Does sertraline seem to improve BBB penetration? 

Thanks for the input!

24 Questions to Ask Your Doctor

Which probiotics to choose

Does anybody use any probiotics containing casei? If so what brands products?

Potassium Channel Blockers

http://www.oncotherapynetwork.com/central-nervous-system-cancer-targets/potassium-channel-blockers-show-promise-treatment-brain-tumors?GUID=027DE295-0400-4A2D-85EA-A43E10BF48F7&rememberme=1&ts=15092015

Not specific to GBM's but of interest

SurVaxM

Just a heads up on this vaccine.  http://www.oncotherapynetwork.com/central-nervous-system-cancer-targets/experimental-vaccine-therapy-glioblastoma-continues-show-promise?GUID=027DE295-0400-4A2D-85EA-A43E10BF48F7&rememberme=1&ts=15092015

Aspirin (or Celebrex) synergize with anti-PD-1 therapy in melanoma mouse model

Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity

(This study is also open access and can be dowloaded as a free PDF from the link above)

In this study, immunocompetent mice bearing melanoma syngrafts were treated with either aspirin (in the drinking water), or an anti-PD-1 antibody (similar to nivolumab or pembrolizumab), or both drugs combined.  Aspirin alone had no significant effect on tumor growth, the PD-1 antibody had a modestly significant effect, while the combination of both agents was highly effective, with over 50% of mice rejecting the tumors.  When a larger number of melanoma cells was injected into a new set of mice, neither drug alone had any effect on tumor growth, while the combination of both aspirin and PD-1 antibody led to tumor regression at day 30.

Similar experiments were repeated with celecoxib/Celebrex (injected intraperitoneally), with similar results, though slightly less effective than aspirin in the melanoma model.

A similar experiment was then carried out using aspirin and the PD-1 antibody, but this time using colorectal cancer cells.  Again, aspirin alone was ineffective, the PD-1 antibody was modestly effective, while the combination was highly effective, with about 30% of the animals rejecting the tumors.

13-cis retinoic acid (Accutane) and thalidomide combination in GBM mouse model

Inhibition of 13-cis retinoic acid-induced gene expression of reactive-resistance genes by thalidomide in glioblastoma tumours in vivo

In this study, nude mice bearing subcutaneous U251 GBM xenografts were treated orally with either 13-cis retinoic acid (Accutane), or thalidomide, or both.  While neither of the drugs alone influenced tumor growth rates, the combination of both drugs significantly slowed tumor growth up to day 18.

I'm not adding this to the library as it is available as a free download from Oncotarget (click on link above).

Toxicities

I've just added a new page (see top panel) called toxicities, to list the experiences of drug-related toxicites that can be definitely or probably attributed to a specific agent.  I'm relying on all of you to report your stories so that this page will be a reflection of your personal experiences, rather than simply a review of the literature.

Memory problems anybody? Cocktail side effect?

My brother has memory problems. He forgets if he ate or not. They gave him one extra week of radiation because the tumor kept growing during the radiation. Also he is on the cocktail now and I am wondering if any of the cocktail ingredients could be causing it. I red something about omeprazole and Alzheimer link. Also people get high by taking omeprazole with some other agents. I am wondering if combining omeprazole with other agents could be causing it. Any suggestions. I am wondering what to take out from the cocktail. The good news is that the last Pet scan with choline looks better than the ct scan from June. The doctor who does not know about the drugs is very surprised. I am worried about the memory though I don't want to make it worse. Is it someting to be expected after radiation or maybe the extra things he is taking like ashwaganda or hepatometer combined with omeprazole? Please give your opinion :)

Thyroid hormones

The thyroid hormone strategy is something that should be more well known.  How many people here have tried this approach?  How long did it take for blood levels of T4 to drop into the therapeutic range as per Hercbergs?

I'll be uploading the most relevant studies to the Brain Tumor Library (in the "Therapies - human studies" folder).  The most recent study is this one:

Medically induced euthyroid hypothyroxinemia may extend survival in compassionate need cancer patients: an observational study

My wifes Cocktail (brain stem, low grade astrocytoma)

Dear All,

Finally I got the time to summarize my wife’s cocktail. I'm a follower of Stephens Astrocytoma option Site from day one.

Before I list the medication that we use right now here is a timeline for her case:

Sep. 2012 -> double vision when she looks to the very far right

Dec. 2012 -> MRI scan -> non-enhancing mass in the brain stem

Feb. 2013 -> light left side weakness, start with strict Ketogenic diet (less than 15g carbs per day)

March 2013 -> open/ extended biopsy -> low grade astrocytoma, IDH1 positive, 3% K67, stronger left side weakness as a consequence of the surgery 

May - July 2013 -> radiotherapy with 54 Gy 

October 2013 -> relaxing or the Ketogenic diet (less than 30-40g carbs per day)

Feb 2014 -> symptoms on with left side weakness for 14 days, MRI shows an enhancement within the old tumor mass -> doctors not sure if progression or necrosis, symptoms gone after 14 days without any treatment. We started a week before the symptoms appeared Longvita Curcumin, and stopped it then.

March 2014 -> Start of Temodar at 5 days on 2 days off non-standard dose dense (Tegwondo Regime, 100mg/m²).

March 2014- September 2014 -> stable scans, no significant changes, enhancing part slightly less intense 

September 2014 -> start of cannabis, vitamin D 

February 2015 -> MRI scan, small but significant reduction of enhancing and non-enhancing part of the tumor. First time that the non-enhancing part is changing in size after radiotherapy

March 2015 -> end of Temodar treatment

March 2015 -> change from Ketogenic to more Logi oriented diet (still less than 40g carbs per day) 

July 2015 -> another great MRI scan, enhancing part is gone, non-enhancing part again a bit smaller

August 2015 -> change from T4 to T3 as my wife has hypothyroidism. No problems with the change, blood counts are already in the therapeutical range as per Hercbergs articles.

November 2015 -> New MRI Scan. No changes in the size, stable scan. No enhancing part anymore. Not sure if the enhancing part was completly gone already in July or with the latest scan. I was not able to see it also in July.

March 2016 -> MRI Scan stable. No contrast enhancing. We are very happy with the result.

October 2016 -> Another stable scan. Forgot to enter the update from July. Still on the same cocktail. T4 supression now over a year without any side effect.

Here is the list of our supplements and medications:

Supplement	Product	Dosis per Day	Start of treatment
Maitake	Nutrisan Maitake D-Fraktion Forte	6	mid. 2014
Probiotic	Nutrisan Probiotische Caps Forte	2	mid. 2014
Pterostilbene	LifeExtension pTeroPure	2	end. 2014
Brokolli	Nutrisan NutriSGS	2	mid. 2014
Metformin	Metformin	2	mid. 2015
Berberine	GlycoX 500	2	end. 2014
Sensoril	Nutrisan Sensoril	2	end. 2014
Vitamine D3	Dekristol 25000	1	end. 2014
Boswellia serrata	H15 Gufic	6	start 2013
ECGC Green Tee	LifeExtension Mega Green Tea Extrakt	2	mid. 2014
Melatonin	MELATONIN 10mg	1	start 2014
Zink	Zink	2	mid. 2014
Canabis Oil	CBD:8%;THC:0,27%	40 µl CBD; 1,35 µl THC	end. 2014
T3	Trijodthyronin	0,025 mg	August 2015

We are considering to start also LDN. Perillyl alcohol looks also promissing, but we don't know where to get it in Europe. Suggestions what we should consider in addition are welcome.

She recovered from all symtoms of the suregery and the tumor very well and can live a normal live. We hope that the positiv trend of the last MRIs will continue and that something from our cocktail list is effective.

Fluoxetine, another MGMT inhibitor?

Important new study here which I will summarize on Astrocytoma Options when I have the chance.  Looks like we might be able to add fluoxetine (Prozac) to the list of agents (along with Keppra and disulfiram) that potentially inhibit MGMT activity in brain tumors and sensitize those tumors with unmethylated/active MGMT to TMZ/CCNU/BCNU.  The main limitations of this study are that the tumor cells were injected into the mouse flank (not into the brain), the drug was injected intraperitoneally (not given orally), and the mice were nude (immunodeficient) mice, so potential effects of fluoxetine on the immune response were not taken into account.

Metformin for Low Grade Maintenance or Not?

I have residual, yet stable low grade oligodendroglioma. I'm trying to decide whether Metformin is worth taking or whether it could potentially contribute to a resistant mutation in the future. I've looked for some research but can't find any. Anyone have a theory on this?

Mailing meds

I was trying to mail cimetidine and tons of other supplements to Poland because some are not available there and customs got it. I have no idea if it is legal to mail cimetidine or not. They want proof of purchase for each supplement translated into Polish and signed It will take me days to translate all the invoices from amazon. $500 in supplements and my brother is waiting for it for days already. :(

MRI results

This is the third MRI in a row that showed shrinkage. At some angles the tumor is not visible at all, at some barely visible. My NO said that if he did not know where to look, he would not have seen it.

I truly believe that the cocktail approach works (together with DCA and marijuana oil). I still haven't told the doctor about all these meds I take. Maybe next time :)

Thank you Stephen, Mike, Anna and everyone else who does their research and helps with advice. I feel like I am going the right way. 

Surgery.. what to do

Dad got a 3rd opinion on surgery today.  First two surgeons said no.  Surgery is however an option with Dr. Silbergeld at UW (Seattle) but requires that Dad be awake, and that he name items on a powerpoint during the procedure.  Dad was at about 61% ability to name the objects in our EGG yesterday and the cutoff for the Dr. to schedule the procedure is 60%.  This is not an obvious - yes, you should proceed with surgery decision.  There is risk involved.  There are three spots where tumor is present in his brain and this was the only section that was deemed operable, but again is in the speech part of his brain.  It is possible to make it worse, or to get in there, find that dad can't communicate well enough, and have to shut the whole thing down without any tumor resected.  Does anyone have experience with surgery in this area of the brain or with Dr. Silbergeld?  Dr. Berger is booked through the end of October and I don't believe we can wait that long.  BTW we had stopped Celebrex, Aspirin and Fish Oil in anticipation of a possible surgery.

MJ's in peace

Hi all,

As of Sept 4, we decided to stop all treatments for Minjung. The scan showed that her tumor has grown substantially over the last few weeks, which explains various symptoms that developed recently. We were considering whether or not to pursue chemo+cocktail treatment immediately, but all of the oncologists we met told us that with her physical condition, she won't be able to tolerate a single round of temodar and that it will only increase her pain. The doctor told us that we could put her to sleep until she passes, so she wouldn't feel the pain and suffering at least.  Her family decided that it is the best they can do for MJ at this point and agreed to his offer... and I respect their decision.

Here are some of the things that I would do differently if I could go back in time. Hopefully, it will help anyone who is in similar situation in devising their treatment plan. Her tumor is located at brain stem, which originally made it inoperable. Our initial plan was to implant shunt and start with RT+chemo protocol as soon as possible. However, we had to wait 3 months because the bleeding at her tumor wouldn't stop, which made shunt placement impossible. I kept thinking over and over that if we could start chemo and radiation right away without considering shunt option, we could have had a better chance. During that 3 month period, her condition became worse and her tumor grew... at that point, we literally begged our neurosurgeon to do the surgery because normally, neurosurgeons choses not to operate in situations like this.

Also, if your situation prevents you from doing RT+chemo simultaneously, may be doing radiation first isn't the best move, especially when your best bet is the cocktail approach. Radiation did not stop her tumor at all; instead, it grew. And by the time radiation was over, her symptoms became worse and we did not even have a shot at battling this evil disease with cocktail approach.

I still firmly believe that cocktail approach can produce miracle. Furthermore, GBM patients should try everything to increase their chance of beating this disease at every aspect of life; maintaining positive attitude, exercise, eating healthy food, laughter, releasing suppressed emotions, etc.

I also want to thank Stephen for creating this discussion venue and for helping us out with invaluable advice and information.

Please do not give up your hope.

My prayers are with all of you and your loved ones.

Sincerely,
Hyunsun

Brain tumour diet

Just wondering what sort of diet is everyone doing? I have my hubby (Alan) on a low carb diet, that includes meat(grass fed) and cheese. I thought that was good then Anna mentioned IGF-1 that is connected to some cancers .  Yikes!!

Updated 10/6/15 Cocktail: 63 y/o male with GBM

All - here is the updated list as of 10/6/15.  I've ordered stronger Reishi mushroom capsules so that will cut our pills down by 5 a day.  We're on day 14 and so far he's doing well.  Blood work showed some elevated liver values but nothing concerning and no need to add the Avastin yet.  His speech has improved and walking is a little better, but he shows signs of 'chemo brain' and issues with short term memory and fatigue.

Drug	Dosage	Qty	When
Pterostilbene	100mg	2 tabs	7:30 AM
Keppra	500mg	1 tab	7:30 AM
Dexamethasone	4mg	2 tabs	7:30 AM
Metformin	500mg	1 tab	7:30 AM
Selenium	200mcg	1 tab	7:30 AM
Verapamil	180mg	1 tab	7:30 AM
Depakote	500mg	1 tab	7:30 AM
Green Tea Extract	500mg	3 tabs	7:30 AM
Ranitidine	150mg	1 tab	7:30 AM
Reishi	500mg	6 tabs	7:30 AM
Quercetin	500mg	3 tabs	7:30 AM
Reservatrol	125mg	1 tab	7:30 AM
Omeprazole	20mg	1 tab	7:30 AM
Disulfiram	250mg	1 tab	NOON
Copper	2mg	3 tabs	NOON
Coriolus Versicolor (PSK)	600mg	2 tabs	NOON
Tumeric (NRF2)	600mg	2 tabs	NOON
Curcumin	750mg	1 tab	NOON
Celebrex	200mg	1 tab	NOON
Chloroquinine (Plaquenil)	200mg	1 tab	NOON
Pterostilbene	100mg	2 tabs	NOON
Pterostilbene	50mg	1 tab	NOON
Multi Vitamin		1 tab	NOON
Sulfamethoxazole		1 tab	M/W/F   NOON
Vitamin D3	5000 IU	1 tab	NOON
Green Tea Extract	500mg	3 tabs	NOON
Lycopene	10mg	1 tab	NOON
Maitake	1000mg	2 tabs	5:00 PM
Reishi	500mg	4 tabs	5:00 PM
Green Tea Extract	500mg	2 tabs	5:00 PM
Coriolus Versicolor (PSK)	600mg	3 tabs	5:00 PM
Keppra	500mg	1 tab	5:00 PM
Dexamethasone	4mg	2 tabs	5:00 PM
Depakote	500mg	1 tab	5:00 PM
Metformin	500mg	1 tab	5:00 PM
Ranitidine	150mg	1 tab	5:00 PM
Fluoxetine	20mg	1 tab	5:00 PM
Stool Softener	100mg	1 tab	5:00 PM
Melatonin	10mg	2 tabs	7:00 PM
Zofran	8mg	1 tab	7:00 PM
Viagra		.25 tab	7:30 PM
Temodar	140mg	1 tab	8:00 PM
Temodar	20mg	1 tab	8:00 PM

Questions:
1.  Verapamil - I asked our primary Dr. for more, and told her that I want a total of 480 or 600mg per day.  She instead upped us from 120mg to an extended release 180mg.  Does anyone know if Rich/Ben took extended release or shorter acting Verapamil?  Does anyone else take the extended release?  

Thanks.

Annie

Can we do anything with 1-octanol

There is something like 1-octanol and supposedly in combination with temozolomide it had some positive results on mice but I don't know how would you deliver it. Maybe sniffing.
Here is some article about it.
http://www.sciencedaily.com/releases/2015/07/150727130818.htm

scL-TMZ or scL-P53. Anyone using or know anything about this?

Hi -
Been reading about scL-P53 on PubMed and it appears to be more effective than TMZ.  Asked our NO about it and was told all TMZ is the same.  Does anyone have any experience with the scL-TMZ? I can't find out if it's available or just in trials.  Here are the links:

http://www.ncbi.nlm.nih.gov/pubmed/?term=scL-p53

http://www.ncbi.nlm.nih.gov/m/pubmed/26325605/?i=1&from=glioblastoma 

Thanks.
Annie

CLA administration significantly reduces angiogenesis in the cerebellum.

CLA is found in cheese and dairy products especially grass fed produce. Link for study with rats and CLA.
http://www.ncbi.nlm.nih.gov/pubmed/18456247

Metformin influences progression in diabetic glioblastoma patients

Study abstract here

I haven't read it yet, but already uploaded it to the Brain Tumor Library (Folder 1 human studies -> metformin)

From the abstract: "Interestingly, diabetic patients with metformin therapy demonstrated prolonged progression-free intervals."

I will probably summarize the findings on Astrocytoma Options soon.

Artesunate

Hi,

does anyone know how to best get hold of artesunate? And is it only available as an infusion, or also as tablets?

I have come across this website: http://www.hepalin.com/ but would like to know if there are also other providers of this drug.

Best,

Lars

TMZ and antibiotics

Has anyone been put on antibiotics prophetically along with TMZ?  I am not referring to Minocycline or similar antibiotic used off label, but rather as prophylaxis against infection.  If so, what dosing schedule are you on?

And what with those apricot seeds?

So anybody knows what's going on with those apricot seeds? Are those of any value or not? The study on it was stopped or something like that?

Prolonged blocking of Ezh2 could lead to tumor progression

EDIT: I just edited the post title, to reflect what the article really says, and avoid spreading false information.  Thanks Stephen!
---------------------------------------


Just found this study.

Article

Minocycline and autophagy

Steven

I was looking over the article you posted regarding minocycline and autophagy.  Are the levels of minocycline discussed in this article clinically achievable?  If they are, then we have another variable in the equation regarding when to use chloroquine.  The other variable being zinc.  If minocycline levels discussed in this article are clinically achievable, then how chloroquine is utilized might need reexamination to optimize the possible benefits of chloroquine, zinc and minocycline.

References document in Brain Tumor Library

I've created a document in the Brain Tumor Library simply called References.  This is a selected list of the most relevant studies relating to the drugs and supplements we discuss on this blog.  Clicking on the [PDF] link will take you to the folder in the Library where the study is kept.

This list could be especially helpful to show to doctors and oncologists who need some convincing that there is valid scientific rationale for these drugs that you may be requesting prescriptions for.

What about statins?

So my brothers tumor has high PKB/AKT . As far as I understood Ben states in his pdf that lovastatin can suppress the PKB/AKT. I noticed that somebody in this group is using statin but not with the temozolomide but with another chemo agent. What do you think about adding it to the mix? My brother does have a high cholesterol.

Tumor angiogenesis, from foe to friend

Stephen:
What's your take on this?
http://www.sciencemag.org/content/349/6249/694.short

Sertraline

Stephen

Regarding setraline, do we have any data to go on suggesting a reasonable dose.  CUSP9* is using a high dose, on your site Astrocytomaoptions you mention setting up trials using low dose, which must be based on some data.  Any thoughts on this?  Jeremy is on 50 mg daily.

Update on Minjung's status

Hi everyone,
Hope all of you and your beloved ones are doing well.

Here's an update of my fiance's situation.
Minjung's been very ill for the last few weeks. She had finished radiation about a month ago, but she started to have minor but constant seizures and some problems with body coordination. She's been and still is being treated with steroids but things are just getting worse... and now she is unable to open her eyes (she still can see if we force open her eyelids).
3 days ago, she had another surgery because the doctor thought her shunt wasn't working properly. When she woke up, she could open her eyes and we all thought things were going in the right direction.. until the next day when she went back to how she was before the surgery.
Also, the current anti-seizure med (Keppra) is clearly not working at all.
So we asked the staff to tell the doctor to prescribe valproic acid as her anti-seizure med today. We'll see how the doctor responds to our request...

We want her to start Temodal and cocktail therapy as soon as possible, but every time we bring that up, the doctor keeps saying she's not ready at all for chemotherapy. We're even considering switching to other hospital. My worst fear is that Minjung may not even have a fair chance of battling this disease, which to me was the cocktail approach.



Best,
Hyunsun