Do Toxicities to Intravesical BCG different in India and can it change the Dosage Schedule

• 20 Nov 2020 11:13:40 AM
• |Onco Urology

Dear All,

We have been recently hearing a lot regarding BCG shortage and alternative Treatments to be considered. We are also hearing considerably regarding BCG Unresponsive NMIBC and alternate treatments for the same.

I am providing an article by Sam S Chang*et al (2020 available online from Nov10th) on ‘Side Effects of Intravesical BCG and Chemotherapy for Bladder Cancer: What They Are and How to manage them’. The article is worth reading and understanding.

Most of what has come out on these aspects are from Western Literature and do they equate to Indian scenario. How often do we see Grade 3 and 4 toxicities associated with Intravesical BCG? Most often we see grade 1 and occasionally Grade 2 toxicities. Does this mean that the responses to BCG are different in Indians when compared to Western Countries? There are few articles addressing this issue from Oriental Countries though TB is common even now in these countries and as per the WHO report India has the highest incidence of TB. There are studies from India, especially Madhu Agrawal and few others that a reduced dose of 80mg is as effective as 120 mg and this reduces the associated toxicities. There are some studies which mention that even 40mg can be as effective (CUETO study). Prof. C Chinnaswamy has opined that he has never used more than 40mg/dose and have never regretted (personal communication).

An article addressing this issue as to Intravesical BCG usage in India (South Indian Population) has been brought out by Ginil Kumar et al in 2019. They have addressed this aspect in detail and have opined that ‘maintenance therapy does not enhance the therapeutic effects of BCG in patients who respond favourably to 6 weeks of induction. He opines that most born after 1948 in India did receive BCG as a vaccine for TB and the inherent Immunity developed could be a reason for the difference.

https://journals.sagepub.com/doi/pdf/10.1177/1756287219833056

This is an aspect that we have to consider when dealing with NMIBC as this appear more common in India than even P ca though we talk about P Ca more than B Ca.

With warm regards,

Venu

Comments(6)

• 

  Venugopal P

  20 Nov 2020 11:17:13 AM

  I am providing the article of sam S Chang on Side effects as mentioned earlier as PDF.

  Venu

  View Document

• 

  Dr. Roy Chally

  22 Nov 2020 04:23:00 PM

     Ginil Kumar’s paper is a retrospective study. This has many limitations. In this paper the incidence of recurrence and progression in 2 yr follow up for NMI bladder carcinoma in our population after BCG is the same as reported in literature. This shows that the disease behaves in the same manner as in rest of the world with intravesical BCG institution. Ginil concludes in his paper that maintenance dose of BCG is not beneficial. The numbers in each arm and duration of follow up are not adequate to draw this conclusion in this retrospective study. To draw a different conclusion from what is in literature, on whether maintain dose after induction has a different outcome in our population, needs more patients in prospective studies with longer follow up. 

               The review paper on this topic does not compare the results of BCG induction only and combination with maintenance therapy. Side effects of intravesical BCG therapy and its prevention and treatments are well covered. 

   I started with 120 later came down to 80mg and as toxicity was still high, now I use only 40mg BCG for intravesical instillation. The review paper also recommends such

  reduction in dose of BCG, if toxicity is observed. 

• 

  Dr. Roy Chally

  22 Nov 2020 04:23:01 PM

     Ginil Kumar’s paper is a retrospective study. This has many limitations. In this paper the incidence of recurrence and progression in 2 yr follow up for NMI bladder carcinoma in our population after BCG is the same as reported in literature. This shows that the disease behaves in the same manner as in rest of the world with intravesical BCG institution. Ginil concludes in his paper that maintenance dose of BCG is not beneficial. The numbers in each arm and duration of follow up are not adequate to draw this conclusion in this retrospective study. To draw a different conclusion from what is in literature, on whether maintain dose after induction has a different outcome in our population, needs more patients in prospective studies with longer follow up. 

               The review paper on this topic does not compare the results of BCG induction only and combination with maintenance therapy. Side effects of intravesical BCG therapy and its prevention and treatments are well covered. 

   I started with 120 later came down to 80mg and as toxicity was still high, now I use only 40mg BCG for intravesical instillation. The review paper also recommends such

  reduction in dose of BCG, if toxicity is observed. 

• 

  Ravindra Sabnis

  25 Nov 2020 02:11:23 PM

  we see almost every patients having side effects - like burning, frequency which hampers quality of life. Often we have to stop / modify either initial dosage schedule or stop / modify maintenance BCG is certainly a big hinderance  in quality of life of NMIBC . we have now shifted to 40 mg dosage & some cases, gemcitabin - which does not cause debilitating side effect like BCG

• 

  Dr. Anil Takvani

  29 Nov 2020 10:30:59 AM

  Contradictory to Dr. Sabnis's observation,  my experience for intravesical BCG is different. 

  In last 21 years,  practicing at single center with excellent follow up we have not seen much side effects or toxicity of intravesical BCG therapy. 

  500 plus patients treaded with hardly 5 patients dropped prior to completion of therapy. 

  Majority patients tolerated therapy without single side effect. 

  We are using 80mg at present. 

  In properly selected cases it is effective.  Large numbers my patients surviving with recurrence or we could reduce/delayed recurrence where they were offered TUR BT again with repeat BCG therapy. 

  Thanks. 

• 

  Venugopal P

  01 Dec 2020 09:23:32 AM

  Dear All,

  The point raised by Anil is of considerable significance. Many of our patients on Intravesical BCG for NMIBC have minimal side effects and very few have severe toxicities as depicted in Western Literature. Many drop outs of treatment are due to their difficulties to return for the treatment. As I am out of practice at present, I do not know how significant this ‘BCG shortage’ in India is as it is being talked in Western World. My take on this, may be incorrect, is with new drugs being made available, the old (BCG) is being pushed aside stating either non availability or increased side effects. Now there are many articles addressing the role of ICIs in the treatment of NMIBC. To make these important, the old will have to be made inefficient.

  Roy has criticized Ginil’s study as having flaws. There can be no study without flaws and we have to take the essence of what is being conveyed. As Anil has pointed out that in his practice BCG is effective, it mean that the behaviour of BCG on our patients are different from the rest. With India being one of the countries where TB is still rampant, many of our patients have Inherent Immunity developed and the response to Intravesical BCG is good as suggested by Ginil. Though I have not done a formal evaluation of my patients, I tend to agree with Ginil that our patients respond well to Intravesical BCG. I have been using BCG made available from Guindy Institute, Chennai from the late 1970’s. As mentioned in the write up, Madhu brought down the dose of Intravesical BCG to 80mg (as practiced by Anil as well) and Chinnswamy has never given more than 40 mg. In an earlier study by Ashish Kamat, he opined that any dose less than 120 mg (Lamm’s Protocol) is futile. But of late he has come to 40 mg of BCG and mentions that it is sufficient and this down dosing is due to shortage in the availability of BCG.

  We should welcome studies done by us in India as we have diverse ethnicity which will have to be looked at when planning treatment options. I am sure these will reflect in our guidelines that we introduce for us in India and not a cut and paste of what is published by other guideline developers.

  With warm regards,

  Venu