PCV regiment and P-gp inhibitors

Inspired by Ben Williams who used Verapamil on BCNU and later on PCV regiment I was planning to use P-glycoprotein (P-gp) inhibitor like Verapamil during PCV chemotherapy.

Problem is that I can't find any research characterizing alkylating agents such as Carmustine, Procarbazine or Lomustine as P-gp substrates. Am I missing something?

Thank you.

Retinoic acid for reversing immune evasion in IDH-mutant gliomas

I'm still going through the abstracts from this year's SNO meeting and came across this:

https://academic.oup.com/neuro-oncology/article-abstract/20/suppl_6/vi258/5154118
EFFICACY OF RETINOIC ACID IN REVERSING IMMUNE EVASION IN IDH MUTANT GLIOMAS

It's tempting to speculate that Ben Williams' use of Accutane (another form of retinoic acid - namely 13-cis retinoic acid) was part of the reason for his excellent response back in 1995. His tumor was since found to be IDH1-mutant. 

This study used ATRA, or all-trans retinoic acid.

Treatment Options for Glioblastoma and Other Gliomas - 2017 edition

This is the in-depth summary of treatment options that Ben Williams began years ago, and which I have taken over lately.  Download the 2017 update over at virtualtrials.com  , or click here for PDF download.   This can be discussed on Al Musella's BrainTumorTreatments yahoo group .  (Of course comments welcome here as well).

Treatment Options for Glioblastoma and Other Glioma - 2016

I'm pleased to announce that the annual Ben Williams Treatment Options update was published today on the Virtual Trials website.  I've inherited the annual updates from Ben, and had been working on this for the past few weeks.

  https://virtualtrials.com/newsarticle.cfm?item=6140  (for Al's commentary and link to the PDF)

Direct link to the PDF here

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.

when to start tamoxifen

Dear stephen and everyone,
We are now 1 week post radiation..and we r supposed to start ccnu after another 2 weeks..
i am planning to combine ccnu with tamoxifen..and i read that Ben started tamoxifen 2 weeks prior the chemo..

So I am thinking this means we should start tamoxifen now gradually..
what do u think?? Is it safe to start it now with a small dose??

Sarah

Ben Williams - cocktail profile

Ben Williams' treatment summary as it appears on astrocytomaoptions.com.

Ben's tumor was recently determined to be positive for the IDH1 mutation, and positive for MGMT promoter methylation.


  

Information compiled from Ben’s book Surviving Terminal Cancer, and from the summary of his story at virtualtrials.com.


• March 31, 1995. At the age of 50, Ben underwent a subtotal resection of a large (180 cubic centimetre) glioma of the right parietal cortex, and was given an initial diagnosis of anaplastic astrocytoma, which was later upgraded to glioblastoma after a more thorough inspection of the resected tumour tissue. Extensive residual tumour remained post-surgery.
• Radiation therapy consisted of the standard 55-60 Gy to the tumour area plus 2 cm beyond the tumour boundary.
• The first MRI post-radiation showed neither shrinkage nor growth of the tumour.
• June 1995. Two weeks prior to his first round of chemotherapy Ben began taking oral high-dose tamoxifen at a dose of 220mg daily. Tamoxifen treatment was continued until March 1998. Side effects of tamoxifen included blood clots which he treated with Aspirin and long walks.
• July 1995. First round of intravenous BCNU (carmustine) chemotherapy combined with 600mg per day of verapamil taken during the week surrounding BCNU chemo. The verapamil was intended to block the drug extrusion pump mechanism at the blood-brain barrier, and therefore increase the penetration of BCNU past this barrier.
• The first post-chemotherapy MRI showed a moderate degree of tumour shrinkage.
• Between the first and second round of chemotherapy, Ben began taking oral Accutane (13-cis retinoic acid) at a dose of 160 mg per day on a two week on/ one week off schedule (he later reduced the dose to 120 mg per day). Accutane was not taken on the days of chemotherapy. Accutane treatment continued until December 1995.
• Also around this time he added melatonin at 15mg per evening and the immune-boosting mushroom supplement polysaccharide Krestin (PSK) at a dose of 3 grams per day. He continues taking 10mg of melatonin to this day (2014).
• August 1995. Second chemotherapy cycle, this time consisting of oral procarbazine, oral lomustine (CCNU) and intravenous vincristine. This regimen is known as PCV. Verapamil was again taken to improve the brain uptake of the chemotherapy during the week surrounding oral lomustine treatment.
• Second post-chemotherapy MRI showed an “enormous” reduction in the residual tumour.
• Third chemotherapy cycle, PCV.
• Added oral gamma linolenic acid (GLA) at a dose of 2-2.5 gram GLA daily, consisting of 10 capsules of borage seed oil.
• Late November. Third post-chemotherapy MRI again showed substantial shrinkage of the residual tumour.
• Early December. Fourth cycle of chemotherapy consisting of BCNU. Ben decided to switch back to BCNU due to stomach pain caused by procarbazine and neuropathy caused by vincristine.
• January 1996. Fourth post-chemotherapy MRI. No evidence of residual tumour, first “clean” MRI.
• Fifth cycle of chemotherapy again consisted of BCNU, followed by another clean MRI.
• The sixth and last cycle of chemotherapy consisted of PCV with a half-dose of vincristine to increase its tolerability. This was again followed by another clean MRI.
• Many clean MRIs followed, though Ben continued daily high-dose tamoxifen treatment until March 1998.

Ben Williams supplement list for reference

This is a list of supplements and doses that Ben Williams published awhile ago.  I re-post it here for the sake of reference.



Genistein (from soy) : 50 mg/day
Silibinin (from milk thistle): 600 mg/day
Green Tea Extract: 1450 mg/day
Curcumin (from turmeric): 800 mg/day
Resveratrol: 150 mg/day
Lycopene: 20 mg/day
Maitake D-fraction (or PSK) : or 3 g/day for PSK
Melatonin: 10-20 mg/day
Vitamin D3: 5000 I.U./day
Fish Oil: 5000 mg/day


Copious amounts of garlic, berries, cheeries, pomegranate juice, and broccoli sprouts.