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First BCG Maintenance Started: Half Dose 40Mg
Hi All,
Brief History
My father’s Diagnosis:
12 Sep 2020 —> Gross Hematuria
12 Sep 2020—-> USG revealed calcified focal plague like mass in UB
12 Sep 2020 —> CT scan revealed 1.8mm x 0.6mm focal plague in UB
13 Sep 2020 —> Cystoscopy revealed Papillary growth in UB posterior wall and BN and part of Trigone.
14 Sep 2020 —> TURBT for all Bladder Tumor and Uro report wrote Papillary growth near BN, Trigone and posterior wall. Took three sample during TURBT. Entire tumor, Deep Bladder muscles, and prostrate muscles. Uro wrote the size of tumor as 3-4 cm after surgery.
29 Sep 2020—-> Pathology report said , 20-30% HG papillary carcinoma, lamina propria and deep muscles invasion not seen. Also no malignancy detected in prostrate. Pathology report measured 2.2x2x0.5cm tumor.
BCG Induction : Could take only 4 instillations 80mg and 2 doses discontinued due to side effects
23 March 2021: reTURBT and Biopsy Both Clear for malignancy. Uro recommended half dose 3 BCG after 6 weeks22 May 2021: 1st BCG dose 40 Mg in 20 ml saline
Results: No fever, no pain, no blood in Urine, no tiredness, no mood swings.
Side Effect: Urine Urgency and frequent urination. The same side effect as induction course but its only the first day. I hope they will subside in 2 and 3 day.I need some advise in BCG saline concentration: Can we increase the saline concentration from 20ml to 50 ml so as to make it less concentrated?
I am really keen to subside the side effect on this maintenance course as its our first one as Uro suggested that BCG was really effective in our case as was evident in reTURBT and biopsy.Please advise
Thanks and God Bless
Special Thanks to Alan , Sara and Joea73 for your valuable feedbacks every time.
God Bless you all and Respect -
40 Replies
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Hi Bills,
That is a great news that your father reaches the first milestone first. And thank you for taking time to provide your feed back.
Below are a few comments at random.1. The side effects more its indication that BCG is working the way it’s should and more its effectiveness?
There was a clinical trial done in 2003. Its conclusion says “Conclusions: While a correlation between BCG toxicity and efficacy exists, this study does not confirm that BCG toxicity is actually responsible for an improved outcome.” I have also heard a similar comment by Dr. Kyrkreja of MD Anderson more recently when she and Dr. Kamat were answering to questions by patients. Incidentally I know a patient who called the urologist because the patient got scared of seeing big clots of blood after BCG but the urologist told the patient it was because BCG was working.https://pubmed.ncbi.nlm.nih.gov/14499675/
2. He drinks more water in morning that keeps his Urine clear till the evening. After 5pm urine becomes yellowish and he says its slightly burns ( tolerable and lasts few seconds)
This is just my opinion.
Yellow urine means more salt concentration than when it is clear. Your father’s tumor was found at almost bottom of the bladder according to the description of you urologist on the first cystoscopy exam. So, the area of TURBT is exposed to urine longer than other area in the bladder. Irritation indicates that the bladder may not have been completely healed. Salt stings open wound. Have you considered suggesting your father drinking water more evenly through out the day?3. May restart BCG even with 10 mg, which is almost 1/10th of initial dosage of 80mg.
Jack had posted in this regard. I have reviewed Jack’s description of how Dr. Lamm might approach the side effects. He recommended 1/10th in the case. Jacked had attached the protocol for BCG treatment by Dr. O’Donnell. (Thanks Jack). Dr. O’Donnell states “the decision to retreat patients with BCG after they have developed severe BCG cystitis must be made with extreme caution. If you must, wait at least 6 months after all inflammation has subsided and restart BCG at a very low dose of 1/30 -1/100th with 100 MU of interferon-alpha”. So, he even reduces the dose to 1/30 to reduce the side effect but it is supplemented with Interferon Alpha to keep the efficacy high. Incidentally, reduced BCG + Interferon Alpha has been for BCG unresponsive patients with some success. So, 10mg seems to be a good testing restart dosage.
4. Intravesical BCG vs Intravesical Chemotherapy for TaHG.
MD Anderson’s published algorithm (2020) for treating TaHG is BCG induction course ( 6 weeks) plus maintenance for 3 years. I was surprised to see it was different from AUA guidlines, which recommends just 6 weeks of induction course (BGC or Chemo). But, the guideline says if TaHG > 3cm or multiples, it should be treated as high risk. Since the side of your father’s tumor was almost 3 cm, treating it as high risk NMIBC makes sense, so the induction plus 3 years of maintenance if possible is justified. Besides BCG has been working so far.
5. Mitomycin
What your dad had was perioperative chemotherapy, which AUA guideline suggests to be administered within 24 hrs after the initial TURBT if a urologist who does cystoscopy thinks the tumor looks like low grade. This is to kill fragments of the tumor which might have have landed to other parts of the bladder, thus reducing the recurrence rate by 10-15%. I assume that because low risk TaLG is usually treated with cystoscopy surveillance only, the protocol increases the recurrence rate, hence mitomycin is administered. For intermediate or high risk, intravesical chemotherapy or BCG is administered anyway, Mitomycin becomes redundant. My urologist did not do this citing me when I asked the question before TURBT that it was done before but not anymore because it wasn’t effective. I am still not happy about it after 3 years. The reason I pointed out England was I think NA provides several treatment options for BCG unresponsive / Intolerable compared to UK, though in the last 2 years, I have seen posts which a patient in Arizona, and a patient in New Hampshire were put on Mitomycin when BCG became unavailable for maintenance. Anyway, in your case, we often say “If it ain’t broke, don’t fix it”. Since BCG has been working so far, it makes sense to continue with BCG, but carefully taking care of side effects.
Best
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Hi Joe,
Thanks and Thanks again for the concern which you showed in your reply. Respect . By the way my dad will achieve first milestone this month 9th as he completes 1year without any recurrence. I hope this continues for all year to come.( Ameen)
I will answer your reply in phases
1)I am very concerned with your father’s health condition if the last two BCG doses of the maintenance course was the cause. The dose was reduced from the induction treatment, but it triggered severe side effects again even giving 6 months rest.
Yes we reduced the dosage to half(40mg) as compared to induction (80mg) and we stopped BCG after 2 doses. Reason being :
a) We did not want him to have the same severe side effect which he has during his induction and took him 4 month to recover
b) Uro and we decided that we will monitor how his response will be @40mg and after 1st and 2nd dose and then continue to 3rd
dose.
c) I had earlier mentioned and its was suggested by Alan and you ( I suppose ) that my dad’s case falls under intermediate risk , BUT I will consider him in High Risk and use the high risk protocol for BCG ( which is 3 yrs, but we will see how far we can go).
d) Although my dad’s case is intermediate risk( TaHG) but I don’t want any chance go begging, so will make sure he will take BCG till 2 to 3 yrs.
2nd dose of BCG Maintainace showed some side effects and he became weak and lost some weight with urine urgency & frequency, BUT they were not as severe as Induction course. Side effects are reduced to 80 to 90%. He drinks more water in morning that keeps his Urine clear till the evening. After 5pm urine becomes yellowish and he says its slightly burns ( tolerable and lasts few seconds)
2) So, I am concerned that he may experience severe side effects even the dose is reduced further. I know it is something your urologist and oncologist decide with you and your father. But one way is to wait and see. Or, try intravesical chemotherapy.
Yes, We have a plan to further reduce the dose to1/3th or more and I am keen the next BCG cycle he takes all 3 doses, even if I
have to start with 10mg BCG, I will , just to make sure he takes all three, becoz as per Dr. Kamat, dose does not matter , it’s the frequency that matters, so 2 is better than one and 3 is better than 2.I did not ask Uro about the Chemotherapy , but I will and I think he might have thought something else , otherwise he would have
suggested me Mitomycin. My dad has Mitomycin soon after the TURBT last year.
3) The initial diagnosis was TaHG. TaHG is considered intermediate risk, and the standard protocol is one year BCG or one year intravesical chemotherapy. I think the intravesical chemotherapy is mentioned because for TaHG, the efficacy is equivalent. Though the side effects are reported with intravesical chemotherapy, they say it is milder than the side effects of BCG. Mechanism of action to kill cancer cells are different between intravesical chemotherapy and BCG. Chemo agent goes into cancer cells and stops
cancer cells to divide and lead it to death, where BCG elicits our immune system responses and the immune responses kill the cancer cells.
We will see this till our next BCG cycle which is due in Dec2021-Jan 2022. By that time we will complete our second maintenance(
hopefully all 3 doses)
4) If your dad’s side effects are caused by too strong response from his immune system to BCG because it has been primed for BCG, alternative approach may be brought up to your doctors.
I need to understand more on this as I don’t know if it’s a good thing or bad. Is strong response from Immune system good indication
or bad? I heard from Sara and others in the forum that more the side effects more its indication that BCG is working the way it’s should and more its effectiveness. Is this correct ? Please advise on this.
5) Incidentally, I sometimes check BCG treatment in UK. For some reason, they do not talk about BCG dose reduction for BCG intolerable patients. They usually try Mitomycin intravesical treatment. That seems to be the standard protocol for
BCG intolerable besides RC. In US and in Canada, Gemcitabine and Docetaxel Sequential treatment seems to have gained the ground of becoming the first line treatment of BCG intolerable patients. There are people who have been treated with GEM/DOC protocol in this forum. They can share their experience when and if you need to know about it.I would say that my father is not completely BCG intolerant as he has taken induction (4 doses) and maintenance (2 doses). I have many doc friends and they all say that we have cases where the patient even cannot take the 2nd dose of BCG induction and we have to look to some other options. So considering those cases , I see my father far better place and condition. Yes there are side effects which he experiences but we are still trying.
Final Thoughts: Currently my dad is doing better after 2 doses of40mg BCG although side effects( frequent urination) were there and he lost some 4 to 5 kgs. I am concentrating on his diet these days. Had an appointment with dietitian as well. We will continue next BCG and try our best to complete all 3 doses (even if we will start 10mg BCG) and increase it gradually to 20mg ( 3rd dose), that time will tell. We will wait and watch after each BCG dose in next BCG cycle.Finally I thank you for your immense knowledge and research which you are doing.
Respect and God Bless.
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Hi Bills,
I am very concerned with your father’s health condition if the last two BCG doses of the maintenance course was the cause. The dose was reduced from the induction treatment, but it triggered severe side effects again even giving 6 months rest. So, I am concerned that he may experience severe side effects even the dose is reduced further. I know it is something your urologist and oncologist decide with you and your father. But one way is to wait and see. Or, try intravesical chemotherapy. The initial diagnosis was TaHG. TaHG is considered intermediate risk, and the standard protocol is one year BCG or one year intravesical chemotherapy. I think the intravesical chemotherapy is mentioned because for TaHG, the efficacy is equivalent. Though the side effects are reported with intravesical chemotherapy, they say it is milder than the side effects of BCG. Mechanism of action to kill cancer cells are different between intravesical chemotherapy and BCG. Chemo agent goes into cancer cells and stops cancer cells to divide and lead it to death, where BCG elicits our immune system responses and the immune responses kill the cancer cells. If your dad’s side effects are caused by too strong response from his immune system to BCG because it has been primed for BCG, alternative approach may be brought up to your doctors. Incidentally, I sometimes check BCG treatment in UK. For some reason, they do not talk about BCG dose reduction for BCG intolerable patients. They usually try Mitomycin intravesical treatment. That seems to be the standard protocol for BCG intolerable besides RC. In US and in Canada, Gemcitabine and Docetaxel Sequential treatment seems to have gained the ground of becoming the first line treatment of BCG intolerable patients. There are people who have been treated with GEM/DOC protocol in this forum. They can share their experience when and if you need to know about it.
best
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Surprise. I just received a reply from Dr. Lamm regarding different CFU on each BCG production batch. Below is the reply.
“Yours is a good question, and your suggestion is logical. The dose is based on weight of the organisms, and the colony forming units is the best estimate of the number of viable bacteria. Unfortunately BCG clumps and does not separate like most bacteria. The number of bacterioa in the colony forming units varies widely, hence the variation in CFU per batch.We and others have demonstrated efficacy of non-viable BCG. Once immunity is established, heat-killed organisms can elicit a response similar to live organisms. Studies trying to look at CFU and response (CFU based on, for example, length of time since production) have not been very successful.
With the shortage, especially, I think it is best to keep the standard we have established.”
So, if I understand correctly, in theory, CFU gives the best estimate of the number of viable bacteria but in practice, there are other factors which affect efficacy and side effects of BCG treatment. In clinical environment, the treatment is based upon the evidence which requires studies involving many patients. CFU related studies for BCG treatment have not successful to prove that it should be used as a measure its effects to the efficacy and the side effect, so we should continue to use the standard (dose based approach).
It is very interesting Dr. Lamm mentions even dead( killed by heating them) BCG bacteria can elicit immune responses similar to by live BCG bacteria once immunity is established. I am not sure what is its’ implication to BCG treatment. A Spanish team reported – Feb,2021 that heat killed BCG bacteria initiated NK cells (natural killer) anti tumor activities. In the study report, they counted how many live+dead bacteria in a Merck Onco-Tice vail. OncoTICE® contains 2–8 x 108 viable BCG per vial, according to the manufacturer’s information but the total number of mycobacteria measured by flow cytometry was 5.95x 109, thus, only around 10% of mycobacteria present in the vial were alive after reconstitution in buffer. So, they have found 10 times more dead BCG bacteria than live bacteria in a Onco-Tice vail. Also the study reported that heat killed BCG bacteria invokes our immune system. If dead bacteria invokes our immune system, CFU alone is not enough to determine the expected efficacy and the side effects.
best
https://www.frontiersin.org/articles/10.3389/fimmu.2021.622995/full#T1
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Re: Dose reduction and CFU
I did not get a reply but I got a reply from another well known urologist. I am afraid that I cannot disclose the name as it was a private email exchange. Below is his response.
“There is wide variety in the number of bacteria (ie CFU) in each batch – but the bottom line is that it appears to work well regardless of that variability. There is probably a minimum number of BCG needed for effect – but that minimum lies below 1/3 of what is in a regular vial. I would not get hung up on theoretical possibilities of numbers – but would stick to clinical trial evidence.
We know that full dose is slightly better than 1/3 dose for intermediate and high risk NMIBC. And we know that 3 years of that full dose is better than 1 year for high risk patients but not intermediate risk patients. We know also from the important trials that dose reduction does not actually reduce side effects – so it is something we do despite dubious evidence.
Bottom line: dose reduction represents a slight compromise in efficacy, but is likely better than scrapping BCG all together.”best
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Hi Sara, thank you very much for providing very detail recollection of your journey with BCG treatment. It is very good data to compare for other patients to compare wit their experience
Thanks Alan for sharing your own BCG experience. I often see the name of Dr. Lamm pops up here and then as the guru of BCG treatment. So, sounds like you had a good urologist. So, I was reviewing again what Dr. Kamat said in his 2019 webinar – “Predicting Response to Intravesical Immunotherapy with BCG”. One of rationales of 6 weeks + 3 weeks rather than 6 weeks + 6 weeks is based upon Dr. Lamm’s study on immune responses, i.e. IL2 protein in urine during BCG treatment. The number of IL2 gradually increases and it peaks at the 6th dose. Then wait 3 months, which I assume it was, another 6 weeks BCGs were administered. They found out that IL 2 counts gradually increases from till the 3rd dose, then it drops at the 4 dose and continue to drop till the 6 dose. I have heard another urologist saying that our immune system get exhausted if BCG is given more than 6 weeks straight. BCG for bladder cancer was first attempted early 1970s by Dr. Molares of Queens’ University in Toronto, Canada. He said that the reason why he administered for 6 weeks was simply because when he ordered BCG vaccines from a BCG vaccine lab, it was delivered 6 vial as a set, and later on some study showed that 6 weeks gave the best result.
In terms of side effects, majority of those who have to stop BCG happen in the induction course, and if patients can get through the induction and the first maintenance (3 weeks), they usually will complete the full 3 years BCG. So, urologists should pay attention especially the induction course and the first maintenance course and manage the side effects so their patients can get through it, so another urologist (associate professor) explained to other urologists and residents in a university hospital. The urologist mentioned Fluoroquinolone antibiotics are a class of medicines that kill bacteria and fight infections. Ofloxacin which belongs to Fluoroquinolone group was mentioned as mentioned to treat rather severe BCG side effect, citing a study done in France in 2006.
The study compared BCG only group and BCG+Ofloxacin group. Ofloxacin was given 6 hrs and 12 after BCG instillation. It did not reduce minor side effects (grade I symtoms), but reduced Grade 3-4 symptoms. Greater number of patients were able to compete the treatment with BCG+Ofloxacin. There were no effect on efficacy. It is a bit counter effective because Ofloxacin kill bacteria and BCG is bacteria, which we need to infect the cancer cells for immune system to kill cancer cells. But the study says it will reduce severe side effects, yet the efficacy is not affected. The speaker is Dr. Alan So, associate professor of department of urological science of University of British Columbia, Canada and he is a clinical urologist at Vancouver General Hospital.
In terms of how many patients can actually complete 3 years BCG treatment. Alan was correct in saying that only 16% of the patients completed a fully three year course of BCG. But that was before, now is different, so Dr. Kamat says.Dr. Kamat says ” This is important because urologist will often just stop BCG at a arbitrary time point claiming that the patient cannot finish the course of BCG,. This was true in 1990s because we weren’t smart enough actually recognize little things we can help our patients, like using aspirin for example or using anti-spasma or stretching out the interval between bcg, So back when the trials were done the SWOG protocol for example, only 16% of the patients completed a fully three year course of BCG. Today however, less than 10% patients discontinued due to toxicity because urologists got smarter. They know how to manage side-effects, there are more drugs available for us to use, and patients have gotten a little bit more smarter as well, so they are motivated to get the complete the full treatment.” But also, I think there are about 15% of patients who have to halt the BCG treatment because of side effects. Dr. Kamat was referring EORTC study 30962.
In terms of reduction of the dose vs reduction of side effects, EORTC study 30962 was launched in 1996 in intermediate and high risk non-muscle invasive bladder cancer patients to determine if one third dose is as effective as full dose BCG, if one year of treatment is as effective as three years of treatment and if one third dose and one year of treatment are associated with less toxicity. After the accrual of 1355 patients and a median follow up of seven years, it was found that one third dose BCG was not less toxic than full dose and that three years of maintenance was not appreciably more toxic than one year of maintenance.
Sara mentioned 1/3 eased her side effects to the extent that she was able to continue the BCG. The large study showed 1/3 did not reduce the side effects, not as much as 1/3 for sure. I recall that Dr. Lamm mentioned 1/10 or even 1/100 is okay if it helps the patient continue BCG treatment. But 1/100 will have the same efficacy. 1/3 will according to the study. In this context, Dr. Kamat showed the result of another study, testing the efficacy of 1/3 and 1/6 and mitomycin. 1/3 gave the best efficacy, 1/6 gave lower efficacy, but better than mitomycin. This study indicates that reducing the dosage even to 1/6 is better than changing to intravesical chemotherapy to deal with the side effects.
Hi Billes,
I have not received a reply from Dr. Lamm regarding dose vs CFU, which one we should use to accurately measure the intended reduction of the side effects. Its been more than a week, so I do not expect to receive the reply.
I am sorry to hear that your dad has not fully recovered from the last BCG treatment. I hope your dad gets full strength back soon.
best -
Thanks Alan, Sara and Joe
I am most fortunate that I found this forum and people like you who has in depth knowledge and experience in dealing and beating this disease. I am confident that what I listen and hear from you are the most important pieces of information I can use to cure my dad.
I will be constantly updating our progress and God Willing good news about our treatment journey.
We have next cystoscope in Oct-Nov and then Dec2021-Jan 2022 Uro would suggest next BCG cycle.
Till that time my dad will have time to recover as last BCG made him very weak and skinny and lost some pounds as well. I will try my best for him to gain some pounds again.
Thanks and Thanks Again to Alan , Sara and Joe
Respect and Regards.
God Bless -
For Bills,
Also, a big thanks to Joea73, Jack and Sara Anne for your research and talent in communicating in a way non-scientists can understand. Had I discovered this site before my BCG I probably would
have done the SWOG protocol that Sara Anne finished. I do believe it is
probably the best course offered even when so many are not able to
complete it. From what I have read very few make it to the 5 and final
year. Others, with their medical team (mostly Europe from what I remember) did
once a month for 12 months if my memory serves me back in older threads.
I do believe an initial 6 is very important.My URO who did study under Dr. Lamm 40+ years ago when they were in San Antonio gave me
the 6 on, 6 off, and 6 more to completion, gave me his reasoning on my
case. First, the tumor was small and probably hadn’t been there very
long. His TURB and second TURB, being high grade revealed only a
papillary growth which is better than with CIS. Basically, he got it
all. Second, every invasive procedure involves some risk from the
cystoscopy, TURB, and BCG. His theory is that my 12 should end any
issues. In retrospect, Sara Anne’s regimen I might have asked to do
more. However, the second 6 had more intense side effects from urgency,
burning and fatigue. By numbers 10, 11, and 12 I could not retain the
BCG for more than 25-30 minutes which also might have told me more
treatments would be a waste. So, who knows?I am also fortunate at almost 13.5 years free of this. Bills, all I am saying is I believe
in BCG as a very good treatment and it is better than not doing it.Do what you do and tolerate with your Dad. Then, go on with your life. No one is guaranteed tomorrow.
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.
Hi there Joe and Bills!! I will try to answer your questions….some of my answers may be a bit vague since I completed my BCG treatments over 10 years ago!
First, to Bills’ question….there is no set protocol (or dose) for BCG administration. The SWOG protocol is just one. Urologists use whatever schedule seems to work for their patients. My experience was to have 6 induction doses, one week apart. This was followed by one a week every three weeks, three months apart, until two years had passed. I understand that this is one of the common protocols in this country but there are others.
Now to Joe’s questions:
1. When did you experience the first side effect (after the first dose?)
As you know, the side effects are cummulative. The one I noticed even after the first treatment was fatigue. The day or so after instillation I was TIRED. (I am not going to talk about the issues on the day of treatment.)
2. Did your side effects get worse as the number of the treatment increased?
Yes. As I noted above, the side effects are cummunlative. They included the fatigue, which got worse, and urinary urgency and burning. These lasted longer as the treatments progressed.2.5 Did the type of the side effects change?
Not really. Just really started to get “worse.”
3. At what point, did you decide to reduce the dosage? How was 1/3 chosen instead of 1/2 or 1/10?
I don’t remember how far along we were. I went in for my treatment and not only was I uncomfortable (!) but cyscoscopy showed a LOT of irritation in the bladder which was diagnosed as “BCG-induced cystitis,” which simply meant that the BCG had really irritated the bladder. We held off treatment for about two weeks and then continued with a reduced dose.
I believe that the 1/3 dose was selected since it was relatively easy to prepare due to the amount of BCG in the vial. It is important to remember that there is NO scientific reason for the dose of BCG used. When this was first tried in bladder cancer patients and found to work, what was used was what was available. (BCG was also tried in other cancers, most notably malignant melanoma, and found to be ineffective.)4. How much did the side effect reduce by reducing the dosage to 1/3?
This dose avoided severe BCG-cystitis and made it possible to continue the treatments. Other side effects seemed to remain the same.
5. Did the side effect get worse again as 1/3 dosage BCG repeated?
Not really. They were already pretty uncomfortable, but I also really wanted to be rid of bladder cancer so I was pretty motivated to continue. My urologist did tell me that even the initial dose offered protection and that each maintenance dose was “money in the bank.” He said that I could quit any time the side effects became intolerable.
6. How did you manage the side effects? Any medication? Increased water intake?
Occasionally took pyridium. Mostly just felt sorry for myself!!! Now that it is over I am VERY glad that I did it.Sara Anne
Diagnosis 2-08 Small papillary TCC; CIS
BCG; BCG maintenance
Vice-President, American Bladder Cancer Society
Forum Moderator
Hi Joe and Sara,
I would love to hear the answers of the questions which Joe has asked.
@Sara, U had mentioned that you had BCG every three months , doesn’t it every 6 months as per SWOG protocol ? Please advice.
Thanks
Hi Sara,
Thank you for the correction. First of all. congratulation for your successful BCG treatment and being cancer free for that many years.I have a few questions.
1. When did you experience the first side effect (after the first dose?)
2. Did your side effects get worse as the number of the treatment increased?
2.5 Did the type of the side effects change?
3. At what point, did you decide to reduce the dosage? How was 1/3 chosen instead of 1/2 or 1/10?
4. How much did the side effect reduce by reducing the dosage to 1/3?
5. Did the side effect get worse again as 1/3 dosage BCG repeated?
6. How did you manage the side effects? Any medication? Increased water intake?Joe
Thank you, Joe, for the very complete explanation that you provided. I know that many patients will find it quite useful.
Just one point to clarify (and a minor one at that!) I had the BCG induction series (six weeks) and then three-week maintenance doses every three months for two years. I certainly didn’t enjoy this and had lots of irritation and BCG-cystitis with urinary urgency which caused the dose to be reduced to 1/3. BUT I have now been bladder-cancer free for over 13 years so it was really worth it.
Sara Anne
Diagnosis 2-08 Small papillary TCC; CIS
BCG; BCG maintenance
Vice-President, American Bladder Cancer Society
Forum Moderator
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.
https://www.youtube.com/watch?v=eK0C5tFHze8 by Prof. Critty of La Jolla Institute for immunology.
https://www.youtube.com/watch?v=_jwBxZMWrng by Dr. Sehult of UCRI 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.
https://www.nytimes.com/interactive/2020/health/oxford-astrazeneca-covid-19-vaccine.html
https://www.youtube.com/watch?v=GOq8-FR8s1E2. 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.https://www.auanet.org/guidelines/guidelines/bladder-cancer-non-muscle-invasive-guideline
best
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
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.
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