Suspicious scope worried about non-BCG options

Shacky73,

Thank you for sharing more detail experience of your BCG treatment.   I am glad you are being treated highly regarded cancer centers like Moffit and Memorial Sloan Kettering.  

That sounds like really bad reactions from BCG treatment.   I know a fellow who has rheumatoid arthritis has very bad flair which required hospitalization  after the 4th dose in the initial 6 weeks treatment.   His urologist stopped the treatment and he has not received BCG treatment over one year. Luckily,  he has not had recurrence so far.    Then he also had bad flair after the 1st dose of Covid-19 vaccination and has not taken the second shot. 

Many patients have been receiving BCG also get the vaccine for COVID-19 during BCG treatment.   I find different hospitals have different protocols.  Someone in this site said at MD Anderson says its okay to have BCG two weeks after the vaccine.  Another hospital says one week apart is enough.     But they don't experience as severe side effects as you have had.   

Anyway, you are in hands of very good hospitals,   and that is a good thing.

Incidentally, this is how two BCG gurus, Dr. Donald Lamm of  ex University of Arizona and Dr. Michael O'Donnell's  way of dealing with the side effects with BCG. 

Dr. Lamm was the chief investigator of the clinical trial which had shown 6 weeks induction + 3 years of maintenance protocol improved recurrence and progression of high risk NMIBC.  His approach in dealing with side effects is to give very low dose the patient experience minimum side effects, then raises the dosage which patients can tolerate.   So, he was the first one to recommend even 1/100 and try to the whole BCG treatment protocol.  Note that only 16% of patients who participated the clinical trial were able to complete the whole BCG treatments due to side effects.

Dr. Michael O'Donnell of University of Iowa does not offer usually the 3rd year maintenance.  He does not think the benefits from the third year is small and because side effects tend to accumulate such that the longer BCG treatment continues, the harder severe side effects patients experience, he thinks the side effects from the 3rd year maintenance would not justify experiencing side effects.

Dr. Ashish Kamat of MD Andersons says 6 weeks + 3 years maintenance will  give the best befits. He says if patients side effects are managed well, 90% of patients should be able to complete the BCG treatment.   One of his distinct approach is to prescribe Ofloxacin every BCG treatment.  Ofloxacin is an antibiotics and a small clinical trial found it would reduce side effects without affecting the efficacy of BCG treatment. 

 pubmed.ncbi.nlm.nih.gov/16890660/#:~:text=Conclusions%3A%20Prophylactic%20ofloxacin%20decreased%20the,primarily%20associated%20with%20patient%20dropout.

Have your doctor mentioned that immune response, especially T-cells which were invoked by BCG are attacking joints like arthritis ?

Joea73

thank you so much for all that info!  My last 2 three week Tokyo BCG were at half dose.  My MD at Sloan did say they could go down to 1/10.

The last two were extremely painful.  The last had me in fetal position for couple hours.

Then a week or 2 later my left knee swelled up.  Drained about 42 cc’s fluid with steroid and it resolved.  About a week after that my right knee swelled and also had to be drained + steroid.  Then about 10 days later my right elbow swelled and had to be drained + steroid.

My orthopedist said if it was BCG in the knee the steroid would have made it worse.  Sloan did a bunch of tests and got immunologist engaged.  He thought it was likely immune overload so to fact I had COVID vaccine a week before last treatment with second dose the week after.  

Next visit they said no more BCG - history plus scope.  But I think I recall Immunologist saying he would be OK with me getting more BCG.

I would certainly prefer low dose BCG if necessary.  

waiting for cytology and will post when I see it on portal.

Thank you again!!!

Hi Shacky73,

Thanks for posting your experience.  We all learn from it.  In The Paris Reporting System (published in 2015)  If cytology says "High grade urothelial carcinoma"  it is high  grade with 90%+probability, "Suspicious for high grade urothelial carcinoma" 50%+ ," Atypical urothelial cells"  8-35% probability of being high grade.    I think different urologists approaches Atypical in cytology, and it seems your urologist has  taken an aggressive way to make sure, which is a good thing.

 It sounds like you had 6 weeks induction and 3 sets of 3 weeks maintenance treatment, so you have completed the most important part of BCG treatment.  I recall Alan had 6 weeks induction and another 6 weeks treatment as maintenance.   I was a bit surprised to hear that your urologist stopped the treatment because of the reaction, rather than continuing with reduced dose.   I heard Dr. Lerner of Baylor College saying recently that in the SWOG`1602 clinical trial to compare MERCK Tice  strain BCG vs Tokyo-172 strain BCG, had seen effective immune response by reducing the dosage to 1/2.1/3, 1/10, 1/30, 1/100 rather than abandoning potential effective therapy.  But, your urologist at Moffit likely decided giving a break to the bladder was more appropriate.   

Re:  Treatment for BCG Unresponsive.

I do not know if your situation is BCG Unresponsive as BCG has been working over a year and the treatment was stopped because of side effects.    So, you may be categorized as BCG intolerable.  Anyway,  as Alan mentioned, there are a few FDA approved treatment for BCG Unresponsive and there are several treatments which are on clinical trials.  

There are two FDA approved treatment for BCG Unresponsive non muscle invasive bladder cancer.

Valrubicin- VALSTAR(R)  approved in 1998.     Approved for BCG Unresponsive CIS.  So, this drug may not be applicable for BCG Unresponsive for T1HG.   Anyway, this drug was not that effective such that though of 90 patients 19 (21%) had a complete response, including 7 who remained disease-free at the last evaluation, with a median followup of 30 months.  

Pembrolizumab - Keytruda (R) approved in 2020.  Pembrolizumab is systemic immunotherapy drug.   It is administered also via vein for BCG Unresponsive.  The treatment is for BCG Unresponsive CIS and BCG Unresponsive HG.   This treatment was better than Vlrubicin but not as good as expected, less than 20% complete response at 2 years.  So, FDA approved in split decision.  

GEM/DOC sequential treatment.  This treatment did not require FDA clinical trial as both Gemcitabine and Docetaxel are generic drugs.  The treatment was pioneered by University of Iowa team and now have been adopted by many academic hospitals because it is much less expensive than Pembrolizumab immunotherapy drug, better efficacy and less side effects.  Gemcitabine is instilled into bladder first and held for 1-2 hours, then voided, then Docetaxel is instilled into bladder and held for 1-2 hours and voided.  Someone posted that Docetaxel was like water.  Side effects of Gemcitabine and Docetaxel are less that Mitomycin which you had been treated before.
Though BCG relies on immune response to BCG bacteria and BCG infected cells to kill cancer cells, GEM/DOC stops cancer cells to divide and leads to the death of cancer cells.  

Drugs on clinical trials for BCG Unresponsive
There are several clinical trials going on for BCG Unresponsive.  Below are a couple of treatments which are on Phase III trials with good results with high expectation to receive FDA approval.

IL-15RFc by Immunity Bio.   Natural Killer cells (innate immune)  are known to kill cancer cells when they are invoked by BCG.  But, it has been observed that some of NK cells are invoked but do not attack the cancer cells, and those inactive NK cells are activated by Interleukin 15, which is immune system related stimulator.   The result of clinical trial 3 showed 71% complete response rate at 2 years and 48% for HG at 2 years.    It turned out that IL-15RFc alone  is not as effective as Il-15RFC + BCG.

CG0070 is Oncolytic Adenovirus. Adenovirus is virus which causes common cold but toxin which causes cold had been engineeringly removed.    CG0070 selectively enters in to cancer cells and replicate themselves.   It also contains drug to stimulate anti-tumor responses.  More recently,  CG0070 + immunotherapy Pembrolizumab combination improved its efficacy with complete response rate at 12 months to be 89% (n=16/18) at 12 months.    

best

I will keep positive attitude and hopefully it isn’t a return of the CA or CIS.

And if I need radical surgery I know I will be OK as well.