Cocktail question, Fluoxetine or Celebrex?

Dear Stephen and all,

I have a question concerning my girlfriend's father. He is 57 years old. He was diagnosed with a Grade IV, MGMT unmethylated Glioblastoma in the left occipital lobe, September 2018. After the surgery, he received radiotherapy and chemotherapy using VAL-083 in China during 08/11/2018 - 27/06/2019. He had an MRI scan on 20/08/2019 and there is a 17mm*10mm GBM recurrence in the left temporal lobe.

Now his oncologist suggests receiving the standard 5/23 Temozolomide treatment. Since his GBM is MGMT unmethylated, we want to have the cocktail to enhance the performance of Temozolomide for him. He is taking Metformin, Verapamil, Chloroquine and Keppra. We want to choose 1 more medicine from Fluoxetine and Celebrex, which one is better?

Thank you for your help! Best wishes to everyone.

Details of the condition of my father are listed below:

• On 28/09/2018 he had surgery due to a tumor in the left occipital lobe. According to the biopsy, he was diagnosed with a Grade IV Glioblastoma Multiforme, MGMT unmethylated, ki67 70%, IDH1/2(-), 1p/19q non-codeleted, non-diffuse.
• On 08/11/2018, he began to receive radiotherapy and chemotherapy using VAL-083 with a dose of 30mg/m2 IV. But soon he suffered severe myelosuppression and both radiotherapy and chemotherapy are stopped for 2 weeks. After that, the dose of VAL-083 was tuned to 20mg/m2.
• On 24/06/2019, the assessment via MRI is CR I class, complete response (that shows the VAL-083 is effective for him)
• On 27/06/2019, he finished the clinical trial, including 10 cycles of treatment using VAL-083.
• On 20/08/2019, MRI shows that there is a 17mm*10mm enhanced mass in the left temporal lobe (the original tumor was in left occipital lobe).

Yes or no on antidepressants?

Hi everyone,

I am finding some conflicting information on whether antidepressants with seratonin can contribute to progression. My husband is on a small dose of sertraline (Zoloft) every day. Is this something we should hold? I have for now as the dose is very small...

Any natural antidepressants that might be worth trying?

Thanks!
Abby

Levi's cocktail

Stephen, and dear blog visitors, I'd also be grateful if you could review my husband's not so extensive cocktail. Should I increase the dosages or should I add something to the list in your opinion? 

I'm so desperate to help him defeat this nasty disease. I know that I'm too hesitant and that we don't have time for that. My husband was shocked about his diagnose so he don't want to read about the possible treatments and drugs so everything is on my shoulders. I totally understand his attitude although it would be such a great help if he would be proactive because he is the smartest person I've ever met. His NO is a very good professional but absolutely not on board, just SOC. We don't even have the courage to ask for his opinion.

Unfortunately we started the majority of these drugs only after radiochemotherapy (except of Metformin and alfacalcidol). We added Aciclovir and CQ on the last week of the radiation therapy. Fluoxetin and DCA right after the last day of RT. Celebrex only 2 weeks ago.

He weighs 70 kg (ca. 154 pounds) if it matters.

Official:

Medrol 16 mg (chorticosteroid - in Hungary we don't have Decadron) This is one tablet only and I'd like to reduce it by half because we have Celebrex but my husband is hesitant because we only have appointment to the NO on 21/8. He has no symptoms other than extreme fatigue and metallic taste in his mouth.

Prescription drugs:

- Metformin - we recently increased it from 850 mg to 1275 mg (This is 1.5 tablet)

- Chloroquine 250 mg

- Fluoxetin 20 mg (Should we increase it to 40 mg? He is quite depressed even after more than a month on it so it just would be a bonus if his mood would be better.)

- Celebrex 200 mg x 2

- DCA 500 mg x 2 on a 2 week on 1 week off basis. We'd like to increase it to 500 mg x 3 as soon as he finishes his first TMZ cycle. Up until now he has not experienced neuropathy although he takes 1 pill of Milgamma Neuro every other day which contains 40 mg of benfothiamin, 90 mg B6 and 0,25 mg B12. We use the product of DCA Lab.

- alfacalcidol 2,5 mcg

Around chemo days:

- Aciclovir 400 mg x 2 (I'm just guessing what would be the right dosage and maybe he should take it daily, not only around TMZ days.)

- Omeprazole 40 mg x 2

His Canadian friend will bring him cimetidine within a few weeks. I'd like him to take 1000 mg a day.

I've just read about clomipramine here but I suppose that you can't use clomipramine and fluoxetin together. Which one has more benefit in your opinion? Mouse evidence on one hand and lots of anecdotal success stories on the other hand.

My husband never had a seizure so I'm hesitant to give him Keppra although its chemosensitizing properties are very tempting.

I have propranolol and I'm thinking to start my husband on it after the first MRI but I'm afraid to mess with his blood pressure. Based on the etodolac + propranolol trial I hope it can be effective with the standard 5/23 protocol, too. I'm assuming that Celebrex can be an appropriate alternative to etodolac.

Although we have a good relationship with our GP who is helpful enough to prescribe for us the above mentioned drugs, I think that she would be reluctant to prescribe tamoxifen, disulfiram, minocycline or maybe even mebendazole on the long term. What do you think of such providers like Alldaychemist? Is it risky to buy from them? Any personal experience?They even have Valcyte which I haven't been able to convince anybody to prescribe since my husband is seronegative for CMV. He had it once but now he has no active CMV infection.

Non-prescription:

- Genistein  (Soy Isoflavones) 28 mg x 2 (We are not so convinced about it and my husband hates it so I think I'm not going to buy it again.) 

- Silibinin 86,5 mg x 6

- melatonin 20 mg

- ca. 1 dl / 3 oz (?) frozen breast milk except of TMZ days (I know, I know...but it was easy to get it through a reliable relative.)

- propolis (30 drops)

- 1 liter green tea on TMZ days with Omega 3 and 200 mg ascorbic acid 

- 1 teaspoon of home-made ethanolic rosehip tincture daily (except of TMZ days) because of this study http://www.scirp.org/jouRNAl/PaperInformation.aspx?PaperID=23446 

I know Stephen what you think about in vitro results but it's so easy to make and it can't do harm.

During RT he ate tons of lycopene-rich tomato juices and home made rosehip puree and steamed broccoli and broccoli sprouts because of sulforaphane. The latter now he hates so he'll start soon on broccoli sprout capsules. I also give him fresh pomegranate juice almost every day.

As you can see we are not so eager about supplements, they seem a bit unproven for us but I recently ordered Longvida curcumin (although its poor bioavailability), liquid Maitake D fraction, Selenium and CQ10. 

Is CQ10 and Selenium applicable in between TMZ cycles despite their strong antioxidant properties? 

Also, we tried a popular Hungarian medicinal mushroom complex (8 pills contain 150 mg rezveratrol, 336 mg shiitake, 336 mg ganoderma, 336 mg maitake, 336 mg almond mushroom) but he had severe diarrhea even on 2 pills a day so I'm not so confident to order him the Mushroom Science PSK product that everyone uses. I didn't see anybody encountering this problem on any cancer forum. It would be a pity to miss it.

I bought some edible oregano essential oil because of these articles but we don't know how to administer it. First, he tried to dissolve 5 drops under his tongue but it has awful taste. Later he tried to drink 5 drops with water. It's also a very strong antioxidant so maybe it's not so smart decision to use it when he is on DCA. or in between chemo cycles. 

https://www.linkedin.com/pulse/oregano-compound-activates-oocytes-kills-glioblastoma-finley

https://www.ncbi.nlm.nih.gov/pubmed/25965832

We'd like to obtain 1:1 THC-CBD oil, too. Could you please provide me with some reliable resources? A lot of people seem to take it but I don't know where to buy it.

Big thank you to Stephen and this helpful community.

CUSP-ND and Prozac

Stephen, I recently re-read the paper on CUSP-ND at:

http://www.anticanceralliance.com/cusp-nd/

and am a bit concerned at all of the "severe" interactions between Prozac and all of the other drugs in the cocktail (starting on page 104). Particularly it's interaction with celebrex and chloroquine.

My questions are:

1. If you had to choose between prozac and chloroquine, which would you choose? 
2. Moreover, I note that in Kast's CUSP9, he utilizes Zoloft (Sertraline) instead. Was there a reason that the CUSP-ND swapped out zoloft for prozac?
3. Would one be more beneficial than the other if Optune is also utilized along with the protocols?

Selegiline vs Prozac

Quick question:  which is proven to be more effective in overcoming BBB for agents to go into the tumor -- Prozac or Viagra or Selegiline?  I have seen many people including Prozac in their cocktail. However, Ben Williams probably indicated in his latest PDF that selegiline could be more effective. Any insights to help select one? thanks, Jinesh

fluoxetine and ondansetron

Has any one here used fluoxetine and ondansetron at the same time? If so has there been any side effects ? As I've read that it can have serious side effects

SSRI and LEF comments

Steven

Any thoughts on LEF comments:

"There is a chemical made in the brain called glial cell-line derived neurotrophic factor (GDNF). It typically aids the survival of neurons after injury. The problem is that it also helps brain tumor cells survive, and, in particular, gliomas. It also helps tumor cells migrate and invade surrounding brain tissue (Lu DY et al 2010, Song H et al 2006, Wan G et al 2010).

Many antidepressants increase GDNF and thus may help tumor cells survive treatment. A 2007 paper reported that amitriptyline, a tricyclic antidepressant, did so (Hisaoka K et al 2007). Serotonin itself increases GDNF (Tsuchioka M et al 2008). Antidepressants classified as selective serotonin reuptake inhibitors (SSRIs) which increase serotonin levels in the brain, may therefore increase GDNF, increasing tumor survival and helping it spread further into the brain."

My thinking is based on the data available, prozac and sertraline, both being SSRI's seem to have an effect different than being suggested here and at this point the "proof" of negative vs positive effects from these SSRI's is in favor of benefit.

Ahmad's chemo cocktail

Hello Stephen and everyone..
I am sharing Ahmad's chemo cocktail..
Ahmad dx 12 October 2014..we had a recurrence and another surgery last June..
Finished radiation 19 August and started CCNU with a cocktail following Ben William's footsteps.

Drugs:
1.Ccnu
2.Tamoxifen 220 mg/day
3.Chloroquine phosphate 250 mg/day
4.Verapamil 480 mg/day bracketting CCNU
5.Prozac 20 mg/day
6.Lansoprasol, esomeprasole, omeprazole: alternatevely 1 each month..(protocol suggested by Anders: each week begins by high dose then standard then a day off)
7.Aspirin 200 mg/day
8.Accutane (still we did not start it) 120 mg/day 2 weeks on and 1 off except chemo weeks.


Supplements:
Milk thistle 900mg/day
Mushroom PSK 3g/day
Curcumin longvida 3600 mg/day
Omega 3 fish oil 3g/day
Pterostilbene 300 mg/day
Broccoli 1000 mg/day
Boswellia 1200mg/day
Green tea 4g/day
Selenium 200 mg/day
Genistein 5g/day
Garlic 6mg/day
Vitamin D3 2mcg/day
Vitamin C 2000 mg/day

Ahmad is following a ketogenic diet

Ahmad did not have any side effects..except recently when we introduced Prozac..I have the feeling this medication is making restless..and very nervous..I am not sure..
I need feedback from those taking Prozac (fluoxetine)..is this dose 20mg enough? And will the side effects reduce with time? I am also worried when using with verapamil..should I reduce the verapamil to 280 mg??

We will start Accutane after next round of CCNU..
God bless u all..and help us in our battle.

Help on Accutane/PCV interaction

Hi All,
This is my first post so far, thanks to all for the knowledge shared especially to Stephen for the time he spends on this.

My wife was diagnosed 2 months ago with a GBM (mutated IDH1 / no MGNT) , It evolved from 2 full resection (201203-AAG3 / 201504-AAG3). Due to the internal capsule in compromised, there is a high risk of hemiplegia, so NO decided to apply PCV protocol in order to produce some regression that may help the work of the NS in a future surgery, decreasing the chance of collateral damage. Her tumour growth was fast in the last 3 months, but after the first PCV it has been stabilized. At that time we found Ben Williams story, Astrocytoma Options web, so we decided to follow cocktail aproach to create sinergy. She is now in the 2nd PCV cycle and we added Tamoxifen, Verapamil, Celebrex, Metformin and a bunch of suplements like Curcumine, Boswellia, Resveratrol, Fish Oil and a couple more. So now we want to add Accutane but we want to be aware of any possible interactions with PCV and avoid them.

PCV Protocol:

• Day 1 - Lomustine.
• Day 8 till 21 Procarbazine.
• Day 8 and 29 Vincristine.
• 2 weeks off.

Any advice on when she should take Accutane?

Thanks in advance.
Francisco.

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!

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.

Methylphenidate

My doctor prescribed Methylphenidate to help with fatigue. I don't really know whether it helps or it is placebo, sometimes I do feel energetic, sometimes not. Anyway, I don't take it every day. What do you think possible interactions could be with our "standard" cocktail?
Pronunciation

Macitentan (Opsumit)

I have serveral concerns in taking my first 30mg dose.  It's usually taken at 10mg every day for a year.  Not on and off at higher doses.  This study made me feel quite a bit better:

http://www.ncbi.nlm.nih.gov/pubmed/23900878

32 healthy subjects took up to 30mg for 10 days without any side effects.

The second concern is that I want to go up to 60mg/day.  This is a link to the prescribing information which mentions going to 600mg and getting liver damage.  It also says there is data on its use with sildenafil. 

http://opsumit.com/splash/pdf/OPSUMIT-Full-Prescribing-Information.pdf

My first day went well at 30mg.  The only side effects are actually positive.  This drug does do a great job at making it easier to breath.  I don't have any problems.  I do walk aggressively every morning and noticed I'm hardly breathing up the hills pushing my 65lb sled.  I think I started getting some chest pains, so I stopped and breathed a little harder.  It went away immediately.  It made me drowsy, but not bad.  I slept well for the first time in weeks.  I'd say it counter-acted the dex nicely in this regard.  We'll see how the higher doses go.  I'm on 40mg now.

-Seth