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