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.

Drugs to Combine with CCNU

My husband will soon begin CCNU for recurrence. In reviewing Ben Williams' document, I see that Verapamil and Calcium Channel Blockers like nimodipine have some evidence for augmentation benefit; however, the articles I found (both from his references and my own search) are quite old. Verapamil has more drug interactions than nimodipine. Is there any research about these drugs or other potential augmenters which I might share with his NO? (His NO has generally been supportive of repurposed drugs when I can share relevant studies. His NO does not want to combine CCNU with TMZ despite CeGaT study due to increased toxicity.)

Much gratitude and well wishes to all--
S.

Strengthening the effect of CCNU + TMZ

My mom will soon take next course of Lomustine + 5 days of Temozolomide.

To enhance the effect of this combination only these days we want to take also:

1. Disulfiram 500 mg + Copper 4mg + DHA 1200mg / day
2. Verapamil 300-400 mg / day (doses of 40 mg every few hours, so that blood pressure does not go down much)
3. Curcumin Longvida 2000mg, EGCg 2000mg / day
4. Alfacalcidol 2 mg / day
According to this study: https://www.ncbi.nlm.nih.gov/pubmed/27313664
Autophagy enhancement contributes to the synergistic effect of vitamin D in temozolomide-based glioblastoma chemotherapy.

Are there any other ideas that can enhance the effect? I have not forgotten anything?
Since my mother takes Lomustine and Temozolomide according to the Ceteg trial every 42 days, I do not want to miss anything.

In addition to these additives our main cocktail includes:
1. Delagil 300 mg / day
2. Bevacizumab 7,5mg/kg/3weeks
2. Sirolimus 2 mg / day (possibly, it will be reduced to 1 mg because of Varapamil)
3. Telmisartan 80 mg (will be canceled for this period because of Verapamil)
4. DCA + caffeine (will be canceled for this period because of Disulfiram)
5. Inhalation with perillic alcohol (will be canceled for this period because of Disulfiram).
    - After Disulfiram, when we can start inhalation again? Probably need a break.
    - Perhaps, for the effect of Disulfiram it is necessary to take it constantly, and not only in the days of Lomustine + Temozolomide? Perhaps, Disulfiram will not have an effect only in these 6 days?
____________________________

I also found this research:
Lithium enhances the antitumour effect of temozolomide against TP53 wild-type glioblastoma cells via NFAT1/FasL signalling.
2017 https://www.ncbi.nlm.nih.gov/pubmed/28359080
"Temozolomide combined with low-dose Li induces TP53wt glioma cell death via NFAT1/FasL signalling. This represents a potential therapeutic strategy for TP53wt glioma treatment."

However, I can not understand is the wild type TP53 our case?
http://btcocktails.blogspot.ru/2018/02/our-report-oncodeep-what-do-you.html

A difficult choice of treatment for a large progressive GBM after chemoradiotherapy

From some studies it follows that:
- Avastin in the first line increases the quality of life and survival for partially resected GBM;
- combination of CCNU + Avastin is more advantageous than just Avastin for MGMT-methylated GBM;
- I can not also not use TMZ immediately after chemoradiotherapy, especially after CeTeg results for MGMT-methylated GBM;
- low Avastin dose (<3.6 mg / kg / week) with Telmisartan, is more beneficial than the Avastin standard dose and will not be so toxic for use with CCNU + TMZ.

As a result, after sleepless nights, I decided to try this combination:

The cycle of 42 days:

0 day - Verapamil 240mg, Disulfiram 500mg, Copper 4mg, DHA 1200mg
1 day - Avastin 6.5 mg / kg
1 day - Lomustine 75 mg /m2 (+ Verapamil 240mg, Disulfiram 500mg, Copper 4mg, DHA 1200mg)

2-6 days - Temozolomide 90 mg/m2 (+ Verapamil 240mg, Disulfiram 500mg, Copper 4mg, DHA 1200mg, Curcumin 2000mg)

7-41 days - Telmisartan 40-80mg, Disulfiram 300mg, Copper 2mg, DHA 900mg)

15 day - Avastin 6.5mg / kg
29 day - Avastin 6.5mg / kg
42 day - Verapamil 240mg, Disulfiram 500mg, Copper 4mg, DHA 1200mg

+ every day Melatonin/Agomelatin, Berberin, Shark Oil, Oxaloacetate, Honokiol...
If possible, DCA will be added 6mg / kg / twice every day.
If possible, the doses of CCNU and TMZ in the next cycle will be increased.

verapamil and TMZ

Stephen,
. IF I was to take verapamil with temodal do I need to start the verapamil a few days before starting temodal also if that is correct and once that is established can I take both drugs at the same time? Would it effect the absorption of temodal? I wanted to take them so they are both in the system at peak plasma times. From what I've read the  time to peak plasma concentration for temodal is 1 hour, half life 1.8 and Verapamil immediate release is 1 - 2 hours for  and half life is 2.8 to 7.4 hours Verapamil extended release with food is 12hours to peak plasma concentration and without food 7 hours. as per link below.

I have both immediate release and slow release but not sure how Alan will respond so not sure if we'll end up taking the SR or the immediate release. Do you know what the best time frame to maximise  Verapamil's multidrug resistance effect along with Temodal for both slow release and immediate release would be.
http://www.medsafe.govt.nz/profs/datasheet/v/VerpamilSRtab.pdf

Verapmil has anti viral activity against CMV and other viruses

 Even though I don't know the dosage and it was cultured in human embryo skin muscle cell it is still exciting...... I know of 2 people who have used verapamil daily (for a year) as part of their cocktail and are still doing great. Rich is one of them.
Using Verapamil alone resulted in a 10-fold inhibition and papaverine resulted in 18-fold inhibition of CMV but combined the inhibition was 112-fold inhibition....

Seth starting swallowing Verapamil and Papaverine.

Ok I'm done. The link is below

Abstract

The disclosure demonstrates the inhibition of replication of human cytomegalovirus (HCMV) in cultured human embryo skin muscle cells by two separate subclasses of direct-acting smooth muscle relaxing agents alone or in combination with each other. These two subclasses are characterized mechanistically as calcium influx blockers (or calcium channel blockers) and cyclic nucleotide modulators. More specifically, the class of calcium influx blockers is exemplified by the drugs verapamil (and methoxyverapamil), nifedipine (the prototype drug of 1,4 dihydropyridines), and diltiazem. The class of cyclic nucleotide modulators is exemplified by the drugs isobutylmethylxanthine, papaverine (and its synthetic analog dioxyline), forskolin, and sodium nitroprusside. In addition, the present disclosure demonstrates that agents from one class, e.g., a calcium influx blocker, act synergistically when used in combination with agents from the other class, e.g., cyclic nucleotide modulators. The calcium influx blockers are shown to act synergistically when used in combination with alpha interferon. In further embodiments, papaverine family member agents are shown to exert antiviral activity synergistically with antiviral nucleoside analogs.

http://www.google.com/patents/WO1987007508A1?cl=en

Last day of chemo... pills to stop?

I can hardly believe it, but today is Dad's last day of chemo (!)  Re-reading my notes, I believe we can now stop some of the medications until we start up our 'maintenance' round of chemo in about a month.  Here is my initial list - highlighting pills I believe we should now stop.  Would love feedback.  Stop cold turkey?  Taper?  Am I stopping something I should keep in the interim between chemo rounds?  I don't want to overlook something critical.  I intend to re-introduce Depakote and Verapamil a week before we begin chemo again.

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

Thanks.

Annie

Would verapamil make Newcastle virus more effective?

We are planning to the the NewCastle virus. Would verapamil make it more effective?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2890100/

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.

Verapamil

Has anyone had trouble with taking Verapamil?  My son's bp has not been under good control since starting verapamil, but we've wanted to stay on it for the anti-cancer benefits of disrupting the BBB.

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

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.