First BCG Maintenance Started: Half Dose 40Mg

1 month 21 hours ago #60913 by joea73
Hi Bills,

I am like any bladder cancer patient just trying to understand things as my urologist is so busy and has no time or interest in explaining to me "why"?   But, mostly I get information from the internet like many others.  I try to comsume the information before I post it.

1. mRNA vaccine

 Though this is the first time that the FDA had approved mRNA based vaccine and it is still for emergency use, mRNA based drugs are not new.  Both Moderna and Biontech have been working on mRNA based drugs over 10 years.  Moderna had been working on mRNA based drug for rare disease but also as vaccine for such as Zika virus, Flu and even cancer vaccine partnering with MERCK -  the manufacturer of immunotherapy drug keytruda.  Biontech  who partnered with Pfizer to manufacture mRNA based vaccine for COVID-19 has been focusing on individualized cancer vaccine which is also based upon mRNA.  So, I tend to believe that  those companies who are very familiar with cancer will not produce cancer causing vaccine.  Also FDA and WHO are  there as gatekeepers to check the safety especially when the vaccines are to be used by everyone in the world.   mRNA is a biological instruction set ( a series of  nucleotides which a ribosome enzyme reads to produce protein inside cytoplasm in our cell.  Then the protein goes outside of the cell though some stay in the cell, but it will not come into the nucleus where DNAs are stored. For the vaccine, after various studies, they determined that the spike protein of the virus causes high response of antibodies to prevent the infection and t cells to kill the virus infected cells. So, mRNA vaccine contains mRNAs for ribosomes to produce copies of the spike protein of the virus. mRNA vaccines by Pfizer-Biotech and Moderna use a little fat bubble ( called nanolipid) to wrap around mRNA and uses it as the transporter to deliver the spike protein mRA into the cytoplasm of the cell ( likely the muscle cells where the vaccine is jabbed).  Once the vaccine produced spike proteins come out of the cell, our immune system detects as pathogen and produces various immunities such as antibodies, B memory cells, T helper cells and T killer cells. The antibodies will be circulating in out body through blood vessels.  So, when the virus actually comes into our body, the antibodies are ready to to stop the virus to infect by sticking to the spike protein and preventing the virus from coming inside the lung cells. For the virus which the antibody missed and infect the lung cell, the T killer cell will be dispatched readily to kill the virus infected lung cell to prevent us from becoming severely ill.   

I have followed Medcram from early on to understand COVID-19  Sars 2 virus.  Medcram is for students who are studying medicine but sometimes medical professional.  Dr.  Roger Seheult, MD himself is an Associate Clinical Professor at the University of Caifornia,Riverside School of Medicine and he is a board-certified in internal medicine, pulmonary diseases and critical care medicine.  So he has been treating COVID-19 patients often in ICU  from the beginning of the pandemic.  He had been explaining almost every day about COVID-19 based on published study papers such as in New England Journals, The Lancer, Nature comparing the data he gets  with his experience in seeing the patients every day and providing various treatments to his patients. There are a few episodes about the vaccine for COVID-19 in his youtube channel. Also sometimes they invite guests.  One guest relating to the vaccine  was Professor Shane Crotty of Critty lab of La Jolla Institute for immunology.  Professor Shane Crotty is a virologist and professor in the vaccine discovery division at La Jolla Institute for immunology.  His team’s early studies on the immune activities in Covid-19 patients gave encouraging prospects of the vaccine.  Dr. Crotty and the other co-counder of Medcram  Kyle Allred gave a webinar of explaining about  the vaccine for COVID-19.  So, I list the link to the webinar.  Also, Dr. Seheult of UCR explains mRNA vaccines in a bit more technical but easily understandable.   Your dad may understand better due  to his background.

    by Prof. Critty of La Jolla Institute for immunology.
    by Dr. Sehult of UCR

I am not sure availability of mRNA vaccines there,. I have read that people in some area are getting COVIDShield vaccine.  COVIDShield vaccine is actually Astrazenaca-Oxford vaccine. Astrazenaca-Oxford licensed SII in India to manufacture the vaccine.  So, Covidshield vaccine uses adenovirus as its delivery system of DNA for spike protein to the cells to produce spike protein and subsequently antibodies and T cells for the virus just the same as mRNA based vaccine.  Adenovirus is usually common cold virus but engineered to be non toxic.  Covidshield chose DNA rather than mRNA to be delivered to cells.   Below is the New York times explaining how adenovirus covid-19 vaccine works.   Dr. Sehult of Medcram also explains the difference between Astrazenca-Oxford vaccine which is the same as COVIDShied.

www.nytimes.com/interactive/2020/health/oxford-astrazeneca-covid-19-vaccine.html


2.    Dr, Kamat

I have notice that Dr. Kamat has empathy and vesting interest in well being of people near birth place.   
But I think he is bound by code of conducts as a medical doctor and by policy of MD Anderson.  In NA, also mitigating professional liability may also prevent a doctor giving any advise unless it is to his or her patient.     I would rather communicate to Dr. Michael O'Donnell of University of Iowa, but not by you directly but rather by your urologist if he or she thinks it necessary because that is what Dr. O'Donnell in 2013 webinar which I had referred previously.


3.CFU

I have looked at a few studies about the efficacy and the side effects of reduced dose of BCG, but none of them described about qualifying CFU of BCG vials they used for the study.   

Do you think your cousin can find out if each vial of BCG has information of lot or batch, and if the prescription label on the vial says CFU? If CFU is not described on the label, can CFU in the vial be traced back by presenting the lot number to the BCG manufacturer, i.e. SII?     

I have sent an email to Dr. Lamm asking if CFU on the label or the production lot should be used as a measure for dose reduction rather than just say 1/3 dose reduction, which I think often understood as 1/3 of a vial.     Lets see if Dr. Lamm will respond.

4.  Is 3 years of BCG maintenance necessary for high risk nmibc (any HG except single,<3 cm TaHG), CIS)

AUA guideline for high risk nmibc classifies BCG treatment into Strongly recommended, Moderate recommended, and Conditional recommendation.   Strongly recommended means that net benefits (benefits vs risk/burden) is substantial.  Moderate recommendation means that Net benefit is modest.   The guide line says a six -week induction course is Strongly recommended for newly diagnosed high risk nmibc, and a clinician should .  The guideline also says in high-risk patient who completely responds to induction BCG, a clinician should continue maintenance BCG for three years, as tolerated. ( Moderate recommendation).   Incidentally, recently FDA and urologists community came up a term BCG un-response, which does not apply to your dad. BCG unresponsive means that high risk nmibc  has recurred after a certain period after the adequate BCG treatment.  They also defined that the adequate BCG treatment is the induction treatment of 5 or 6 and the 1st maintenance of 2-3 weeks.  So, your dad had the adequate BCG treatment though there was a delay for the maintenance due to waiting for healing  the side effects.   I know Allan and I think Sara too had 6 weeks induction course and followed by another 6 weeks treatment, and the cancer had not recurred for many years. 
Urologists often say that they do not fully understand yet  how BCG works for bladder cancer even  BCG treatment for bladder cancer was introduced 40 years ago. They say they use it because it has worked.    BCG therapy utilizes our own immune responses. But not all have the same immune responses and tumor can be different even between T1HG and T1HG.   I know a patient who has autoimmune disease -Rheumatoid arthritis.  In his case had to halt after 4th BCG in the initial 6 weeks course because of severe side effects.  The same patient had severe reaction to the 2nd dose of covid-19 vaccine, which put the patient in in the hospital for 10 days.  So, it seems that many things affect BCG treatment so it needs to be cared personally for each patient, which I think you, urologist and oncologist are providing.   

www.auanet.org/guidelines/guidelines/bladder-cancer-non-muscle-invasive-guideline

best
  

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1 month 2 days ago #60912 by Bills
Hi 

I am from actually from Kashmir ( disputed area in India) but living and working in UAE.  Since BCG is abundantly available in my state of Kashmir so I shifted my dad to Kashmir for BCG instillations. I could have arranged it in UAE also but it need to be ordered as they don't keep stock.
One of my cousin is a Medical Distributor , so he arranged for me all BCGs used till now. I discussed with them concept of CFU and they understood it and even told me that they can preserve for me BCG from one receiving lot. That's the reason , I asked a question if that can help my father to reduce the side effect of frequent urination.

I am sorry to hear that you are facing issues in getting the BCG. Please convey if I could be some help in the same matter.

Thanks to All
Respect 
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1 month 6 days ago #60909 by hamondale
Replied by hamondale on topic First BCG Maintenance Started: Half Dose 40Mg
Hi. I am curious as to where your father is receiving treatment? Your comment "I generally buy BCG from a distributor rather than a retailer pharma" definitely got my attention. I am in the US and am experiencing a delay in treatment because of the BCG shortage.

Your father is very lucky to have someone like you advocating for him.

Wishing you both all the best.
Pat
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1 month 1 week ago #60905 by Bills
Hi Joea

Thanks for a detailed explanation as always. Alan rightly said you are a scientist in this field. 
  1. Yes my father is a professor in Biology by profession and was CEO for education dept. in his latter years of services. He knows all things going  in through the human body. I cannot stop him researching and exploring things. He told me that vaccine has a effect on mRNA and DNA synthesis and effects the body at the DNA and hence the gene levels. He also related Ca is caused by change in DNA and genes and hence he is reluctant in taking vaccine. But I will persuade him sooner as he turns 76 now this July.
  2.  Coincidently I called M D Anderson's hospital last weeks and wanted to check if I can get an online appointment with Dr.Kamat. They took all my details and said we will get back. They came back saying that we don't do online appointments and patient should be here and we should evaluate him first to proceed further.
  3.  You are very right in explaining the side effects of BCG and your CFU concept is a perfect example for cause of the side effects. In fact one of the webinars of Dr. Ashish Kamat , where he explained the BCG intolerant patients and said that its not the strength of dose of BCG which cause the issues , its the CFU/mm which is the main cause of intolerance with BCG. More the CFU of BCG more side effects.
  4. As you said CFU remains same in the lot , I can arrange the next two BCGs in the same slot. I generally buy BCG from a distributor rather than a retailer pharma. I can ask him to the details about the lot and can he preserve for me the same BCG for my next maintenance doses. I think this can be done as the distributor is known to me well. If I get the same lot BCG in my dad's next two maintenance doses , do u think it can make a difference?
Rest I wish everyone here a lot of happiness and healthy and long life. 

Thanks to You, Alan and Sara

Regards and Respect 
  

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1 month 2 weeks ago #60891 by joea73
Hi Bills,

I understand the concerns your dad has toward the vaccination because he had learned from somewhere that cancer is the result of gene mutations and his experience with bladder cancer has been hard due to the BCG side effects.  I have the same problem with my sister who is 80 years old and lives overseas.  Because  her family doctor said "just do it"  when she asked if the vaccine did not affect her existing condition.  The concern I have is that the old age is high risk. We witnessed that in the beginning of the pandemic, many old folks died in long term care facilities where young people got hardly hospitalized.  Center of Disease Control (CDC) says once infected, the death rate of age 65-74 is 95 times, 75-84 is 230 times higher than that of age 19-28.  The rate increases to 600 times for people of 85+.  This is the data from actual cases.  This is the risk you father and my sister is taking until vaccinated.   In terms of your dad's concern if the vaccination changes DNA, the CDC says it is a myth.  You will understand why DNA will not be affected by learning how RNA based vaccines, such as Pfizer and Moderna work. and how adenovirus based vaccine such as Astrazeneca and J&J work.   This is explained in the CDC site. 

www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-age.html
www.cdc.gov/coronavirus/2019-ncov/vaccines/facts.html

In Canada, Pfizer and Moderna RNA based vaccines are used now.   Astrazenaca was administered early but not now.

In UAE, I have noticed that UAE has approved Pfizer, China's Sinopharm and Russia's Spuotnik V.  Fully vaccinated is 72% and 80.5 at least one dose of the whole population.  That is very high vaccination rate. Because UAE also vaccinated seniors as  priority, the seniors who were vaccinated must be very high though I do not have access to the actual data.

Incidentally,  Sinopham and Sputonik V use adenovirus for its vaccine similar to Astrazeneca,  DNA will not be affected.   


If you follow Dr. Ashish Kamat, you will pretty much understand the current status of various diagnosis and treatments for bladder cancer.  So, that is good.

I do not know if Dr. Michael O'donnell will respond or not.  I merely stated what he mentioned in Q&A session in  his webinar.  Please not that he specifically mentioned the question must come from a doctor.

BCG vaccine production quality control is defined by WHO.   BCG is live M. Bovis (live tuberculosis causing bacteria to animals such as cows) so it is difficult to control production precisely.  So, WHO allows a certain variability in the final product.   For example, BCG vaccine is produced by batch ( or lot) - some says in a keg just like beer, and one batch to the next may have different amount of bacteria concentration.   FDA MERCK's TICE'  each vial contains 1 to 8 x 108 colony forming units (CFU) of BCG which is equivalent to approximately 50 mg wet weigh.  FDA knowledges that MERCK TICE BCG can have 1 to 8 times difference between one batch to another.  FYI,  The size of one BCG bacteria is 1.0 - 4.0µm or avg 0.002 mm long by 0.2 - 0.3 or avg. 0.00025 mm wide.   1mm x 1mm CFU can contain 500 bacteria.   I do not know average size of CFU of BCG, but it means that each vial of TICE BCG has 1 to 8 x 1011 bacteria or 100 billions to 1 trillion bacteria.   As Dr. O'Donnel says in the webinar. much of them are washed out but so many bacteria are administered into the bladder with on BCG treatment.   The point I want to make is that when we manage patient side effect by reducing the dosage, we actually need to make sure that BCG with reduced dosage with intent to reduce the side effect must come from the same batch (or lot) of BCG which caused the side effect initially because FDA allows the number of BCG bacteria can vary 1 to 8 times between batches ( or lots).  In other words, if a patient who had side effects by BCG from production lot A with 1x108 CFU, the patient gets 3 times more bacteria from 1/3 dose of BCG from the production lot B with 8x108 CFU.   In practice, it is highly likely that the patient gets BCG for reduced dosage from the same batch which BCG had caused side effect.    But, when the timing of the BCG which caused side effects and the reduced BCG is wide apart, such as 6 months, those BCG could come from different lots with different CFU.  So, a care must be taken to make sure that reduced BCG is actually reducing the number of bacteria administered into the bladder.   In case of SII ONCO-BCG,  the variability of bacteria concentration in a 40mg vail is 1x108 to 19.2x108 CFU (see below link for  SII prescription list).  It means that from one to another lot, the number of bacteria in a vail can varies from 100 billions to 2 trillion or 20 times difference.   Because the time between the last BCG administration to you dad and the next administration, if they are going to try with 20mg, is over 6 months. it is important that the production lot number are the same.  When I look how SII-ONCO-BCGs are shipped to different countries, they do not ship them in large quantities. I cannot access to the more recent shipping records. For example in July,2016 50 40mg vails and in September 150 mg vails where shipped to UAE.  It does not look like UAE imports 10,000 vials at once and keep them in storage.  So, I cannot predict if the BCG which your dad may receive as reduced to reduce the side effects comes from the same production lot which the maintenance BCG which had caused side effects.   Anyway, I am guessing that  the production lot number should be printed on the label of the BCG vail.   Also it is likely that the hospital you deal with is fully aware of this.

best

www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert---BCG-Vaccine.pdf
www.mims.com/philippines/drug/info/sii-onco-bcg?type=full
www.zauba.com/export-sii+onco-hs-code.html
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1 month 2 weeks ago #60885 by Alan
Bills,

Glad both of you doing well. Also, thanks to Joea for being a great scientist!

DX 5/6/2008 TAG3 papillary tumor .5 CM in size. 2 TURBS followed by 6 instillations of BCG weekly with a second round of 6 after a 6 week wait.
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