Reduced Dose BCG: Why It Might Not Matter

I have found a prequal paper relating on this matter.  I think one of the cause is that the discussion between FDA and urologists to define BCG unresponsive started before the BCG shortage became serious.   The discussion started before 2015 and the announcement of Sanofi's decision to withdraw from BCG business which led to semi permanent BCG shortage was announced in 2016.   They could not think about its implication then.

Anyway,  the prequal paper states "Adequate BCG treatment" which is defined as 5-6 weeks induction course and 2-3 weeks maintenance course.  Incidentally,  I have read somewhere that why 2 or 3 years of maintenance  treatment is not required to be classified as adequate BGC treatment is their recognition of other BCG treatment protocol such as 6 weeks + 6 weeks (maintenance) are being used.        

1.   variation of amount of dosage to mitigate the impact of BCG shortage, recommendation by AUA for the dose reduction to 1/2,1/3 in case of the shortage.
2.   variation of BCG strain :  SWOG - a a National Cancer Institute supported organization that conducts clinical trials in adult cancers started clinical trial to compare Tokyo-172 strain BCG manufactured by Japan BCG Lab and MERCK Tice strain BCG.  There are about 1,000 participants in the  clinical trial.    
3.   variation in timing of BCG treatment : use of different protocols, delayed treatment by shortage, side effects created wide range in BCG timing, so the paper recommends to limit enrollment to those who had adequate BCG over 6-9 months.
4.  patients who had received the treatment for a BCG unresponsive were not eligible for different BCG unresponsive treatment.   The paper suggests the inclusion of those patients to a different treatment for BCG unresponsive if sufficient time elapsed from the first treatment.  

I think understanding of  the inclusion criteria for a clinical trial is important as it will  likely be applied to the inclusion criteria for the eligibility to the drug and the insurance coverage  when the drug is approved and become available for for patients  in general.

The paper was authored by Dr. Roger Li of Moffitt and coauthored by Dr. Seth Lerner of Baylor and Dr. Ashish Kamat of MD Andersons. 

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Thanks Sara.  Thank you also  for giving me an opportunity to participate in a well designed forum platform.  Though I am now on annual surveillance by cystoscopy only, the images of sequences still stay clearly in my mind from the weird guts feeling I had when I first saw painless pinkish urine in the bathroom 4.5 years ago, startled and shocked by seeing red  blood covering the basin in a public bathroom trying to hide the scene from the guys standing next to me for some reason, which led to the visit to ER and eventually seeing  a cauliflower like tumor on the screen and finally had to tell my wife that I had bladder cancer.  I am sure it made my family worried.   For some reason, doing research has become my mindful activity so my mind not being occupied by the thought of cancer constantly.  I have become fascinated by  how super super complex automated factories our body is made of.  I would have gotten much better grades in school if I had studied as much as I spent my time in doing research about bladder cancer.  I am sure that many fellow patients have gone through the same path.   Over the years, I have come to know who's who in the field of bladder cancer.  So I have been following some of them on Twitter.  When I find a new and relevant subject, I do background check and post it.  I think I understand better about my prognosis and calm on the matter till about a few weeks before the next cystoscopy when I start having anxiety.  

A while ago, I sent an email to Dr. Lamm about possible impreciseness of reduced  dose BCG protocol, which is  used to enable a patient with severe side effect to continue BCG therapy.  My question to  him was the product monograph of MERCK ONTICE BCG says that a vial contains 1-8x10**8 CFU. It indicates MERCK guarantee that the vial contains between 100 million CFU and 800 million CFU. CFU (Colony Forming UNIT) is a unit which is used to measure how many bacteria exist.   So, it is possible that a patient who had been treated with the vials containing 100 million CFU and developed severe side effects, and the patient switched  1/3 dose expecting the reduced dose will reduce the side effects.  But a possible scenario is that the vial which is used for 1/3 dose may contain 800 million CFU translating to 267 million CFU which is more than 100 million CFU which was used for the full dose treatment.  Dr. Lamm's response was mathematically true but the BCG vial contains live and dead bacteria so we need to rely on clinical test.     The 1/3 dose protocol has been used also do address BCG shortage and recommended by AUA to be used for maintenance treatment.  But this 1/3 dose protocol is facing some problem for those patients with 1/3 dose regimen are not being accepted by sponsors for their clinical trials for the treatment for BCG Unresponsive.   The report with the link below is addressing the impreciseness of reduced dose protocol and asking the sponsors to include those patients who have been treated with 1/3 dose because of the shortage. 

content.iospress.com/articles/bladder-cancer/blc211648

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