I saw a presentation by Dr. Ashish Kamat of MD ANDERSONS explaining that the reason why BCG is administered thee weeks for maintenance is because the immune response peaks at at 3rd dose, and start declining if the 4h dose is given. They tested the amount of interleukin-2 in urine which regulates CD8 T-cell. CD-T-cells kill BCG infected bladder cancer cells. Declining of interleukin-2 indicates that T-cells are being exhausted. Note that for the same reason, 6 weeks administration of BCG are considered optimum. There are so called memory T-cells. Though most T-cells initially invoked by BCG die 2-3 days after they are invoked by BCG, some percentage of T-cells continue to live. Technically speaking though I do not know how long Memory T-cells live off hand, Memory T-cells give durability of BCG treatment. A case in point, BCG treatment gives about 55% complete response for CIS by initial 6 weeks treatment, but the complete response rate increases to 85% at 9 months without maintenance treatment. This is due to Memory T-cells.
Chemotherapy uses body's ability to lead cell to Apoptosis (Self Death) when a cell division cycle. fails. Gemcitabine interferes the process of DNA replication in early part of cell division cycle and Docetaxel interferes building of microtubules just before the cell divides into two daughter cells. In both cases, it invokes apoptosis, killing cancer cell. Actually kills normal cells too but normal cell do not go into cell division cycle often whereas cancer cells are constantly dividing. So, chemotherapy kills many cancer cells but a few healthy cells. Chemotherapy does not offer durability as BCG does not rely on immune systems as BCG treatment does.
I do not know when and how they came up with 6 weeks initial treatment for intravesical chemotherapy. Intravesical chemotherapy was first used in 1903 and various chemo agent were tried. I see 1995 publication of a study tested Epirubicin for CIS and T1HG. Patients were given intravesical Epirubicin for weekly for 10 weeks without maintenance. In the current AUA guidelines, a six week course of intravesical chemotherapy or immunotherapy is recommended. Also, it says that in an intermediate patient who completely responded to an induction course of intravesical chemotherapy, a clinician may utilize maintenance therapy. It does not say how often at what interval.
Dr. Michael O'Donnell of Univ of Iowa is know as a early guru for NMIBC along with Dr. Lamm of Univ of Arizona. Dr. Michael O'donnell is considered as a guru for intravesical chemotherapy, and devised six new intravesical chemotherapy treatment. Dr. O'Donnell began studying of intravesical chemotherapy combinations over two decades. So, probably we can take the treatment protocol 6 weeks + monthly maintenance as the result of his years of study and clinical experiences which gave the most efficacy with acceptable toxicity.
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