I would be a little careful of putting too much faith in Thomas Seyfried's ideas. If you google him a bit you will find lots of issues with some of his theories. Haven't heard a lot about him lately, but he was quite a "buzzword" with his ketogenic diet ideas a number of years ago.
Diagnosis 2-08 Small papillary TCC; CIS
BCG; BCG maintenance
Vice-President, American Bladder Cancer Society
Glad to hear you were able to reach Dr. Lamm. Thanks to this forum and your postings and other people' postings it seems we were able to connect dots regarding Thermo-chemotherapy and gemcitabine & docetaxel. Refer to regarding non thermal gemcitabine & docetaxel in this forum. https://bladdercancersupport.org/forum/8-non-invasive-superficial-bladder-cancer-questions-and-comments/47198-switch-from-bcg-to-gemcitabine-and-docetaxel.html
Just to put in perspective, BCG therapy for bladder cancer was used in 1975 by Dr. Alvaro Morales of Queen's University in Canada. Dr. Michael O'Donnell of University of Iowa, who co-authored the study of gemcitabine & docetaxel sequential (non heated) treatment for BCG unresponsive is early pioneer for the treatment for non-muscle invasive bladder cancer. Dr. Donald Lamm, who co-authored the study by University of Arizon on gemcitabine & docetaxel sequential (heated) treatment for BCG unresponsive is also early pioneer for the treatment for non-muscle invasive bladder cancer- especially focused on BCG treatment. Below are some of newer generation of urologists who appear often in media on non-muscle-invasive bladder cancer treatment, i.e. Dr. Ashish Kamat of MD Anderson, Texas, Dr. Peter Black of University of British Columbia, Canada, Dr. Arjun Balar od NYU, Dr. Joshua Meeks of Northwestern University in Chicago, IL, etc.
The reason why I mentioned those names that in 2019, Dr. Balar and Dr. Black debated which recently approved treatment for BCG unresponsive is what they would recommend. One is Keytruda which is administered intravenously and Nanofaragene which is administered by catheter into bladder like BCG. We know how Keytruda how it works. Nanofaragra uses adenovirus as a vehicle to deliver the gene intereron alfa-2b into cells. Interferon alfa-2b has been used combined with BCG for those NMBIC patients whom BCG alone did not work.
Adenovirus is common cold virus. Adenovirus cotaining interferon alfa-2b gene penetrates into a cell. The cell will produce a protein interferon alfa-2b translating alfa-2b gene. Then interferon alpha-2b protein kill cancer cells.
Anyway, Keytruda and Nanofaragra showed similar efficacy, though more side effects on Keytruda. But the efficacy was not as good as they had hoped for. The complete response was 53% at 3 month, 24% at 12 month for Nanofaragra and it was 41% at 3 month 19% at 15 month for Keytruda. Anyway, they were aware of the study which reported a good result of gemcitabine and docetaxel. Dr. Black says "the numbers would suggest that it's better than either of these two drugs and it's inexpensive, easy to give, well-tolerated. I think we need to be very, very careful with that data and really need to go with trial data" The link below gives us an access to the video of the debate and trascript.
So,how does kne know which treatment will most likely be more successful?
I have contacted Dr Lamm. I am making arrangements to be treated by him. Thank you immensely for giving me his name and contact information.
I can't begin to thank you adequately for your precious help.
I also have read that cancer cells with high PD-L1 expression tend to respond to immunotherapy. But I also find that it is not quite simple.
I often get confused PD-1 and PD-L1. My understanding is PD-1 is a protein on the surface of immune T-Cell and PD-L1 is a protein on the surface of the cancer cell. If PD-1 and PD-L1 shake their hands, our immune T-Cells will not attack the cancer cell. One type, i.e. Pembrolizumab (trade name is Keytruda by MERCK) of immunotherapy drugs is to put a glove on PD-1 on T-Cell. The other type, i.e. Atezolizumab (trade name is Tecentriq by Roche) is to put a glove on PD-L1 on the cancer cell. Either way, it prevents from PD-1 and PD-L1 from shaking their hands and that make free T-Cells to attack the cancer cell. NCI explains those two drugs more technically.
Pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells. (National Cancer Institute).
Atezolizumab binds to PD-L1, blocking its binding to and activation of its receptor programmed death 1 (PD-1) expressed on activated T-cells, which may enhance the T-cell-mediated immune response to neoplasms and reverse T-cell inactivation. (National Cancer Institute).
In terms of PD-L1 expression, they use Combined Positive Score (CPS). When MERCK was doing a clinical trial for Keytruda, they used a specific assay (stain) over tumor cells from a biopsy. The assay makes cells PD-L1 protein change color. A specially trained pathologist counts the number and cells which changed color and applies the formula CPS = # PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by Total # stained and unstained tumor cells x 100. In the case of bladder cancer, the specimen is considered to have PD-L1 expression if CPS greater than or equal to 10. In 2017, FDA approved Keytruda for advanced or metastatic urothelial carcinoma for patients whom Cisplatin chemotherapy did not work. FDA approval of Keytruda was based upon
clinical trial NCT02335424, Phase II trial of Keytruda which showed patients with PD-L1 expression 10% or more met the objective goal. Because Keytruda is expensive - about $10.000 per dose of 200mg and it requires a dose every 3 weeks it costs $150,000 per year or $300,000 per two years - and there are some side effects, for a patient to qualify Keytruda for advanced and metastatic urothelial carcinoma the patient's PD-L1 expression needs to be 10% or greater. I think this raises some ethical questions. What if PD-L1 expression is 8%? What if the patient is not covered by insurance.
I have attached JPG file, which shows examples of PD-L1 expression. Brown colored cells are stained cells by the special assay ( manufactured by Agilent) .
Left side is PD-L1 less than 10% or CPS <10 and right side is PD-L1 greater than or equal 10 or CPS>=10.