As described in my first blog posts, in 2017, I began a (first) health journey, losing 100 lbs. and reversing type 2 diabetes, and after 30 years, began e-biking (I ride the beautiful hills of East Tennessee).  I joined the Great Cycle Challenge, where tens of thousands of bikers spend a month riding to raise research funds for children’s cancers. I am riding this month for the seventh year.  Although it is devastating to children and their families, due to relatively smaller numbers receives only 4% of federal research funds.  Bladder cancer receives roughly 1% of federal funds. So, like the Bladder Cancer Advocacy Network (BCAN), this activity provides young investigators with the funds they need to advance their ideas that may lead to practice-changing breakthroughs such as that I am benefiting from. Data shows the benefits of exercise for cancer patients, and I continue to bike year-round during my journey.

BCAN discusses exercise and cancer here.
You can find my Great Cycle Challenge challenge story here

 I had a genetic test done after I began my treatment (enfortumab vedotin + pembrolizumab / Padcev+Keytruda).  This treatment performed so well in its phase 3 trial that no pre-testing (e.g. for PD-1 ) is required for patients presenting with locally advanced or metastatic muscle invasive bladder cancer.
I did request genetic testing where I found I had a  PD-L1 CPS score of 10, which indicated that Keytruda should be effective (there is currently no approved biomarker to predict effectiveness of Padcev).
I also had germline testing. This is a genetic test that looks for inherited mutations in your DNA that may increase your risk of developing certain types of cancer. These mutations are present in virtually all cells of your body and can be passed down from one generation to the next. I wanted my daughter to be aware of any mutation that might increase her cancer risk.
The test found one variation in the CHEK2 gene.  When the results came in I met with a genetic counselor who told me that the most recent data suggest a possible increase in breask cancer risk - but that the probability does not warrant any more than the screening which is currently recommended for all women.
Germline testing for cancer patients is currently underutilized - I am glad, for my daughter's sake that my oncologist suggested it.

On Monday, July 29, I had an outpatient procedure at my primary provider - the University of Tennessee Medical Center - to implant a chemo port.  It was my first opportunity to see, up close, interventional radiology equipment from my old employer Siemens.  I didn't see it long - I remember being wheeled into the room and then waking up in the recovery room.  It was not intubated and happy to be under moderate sedation.  A Tylenol the first night after surgery was the only medication I needed.  The picture above was from the following morning.  I need to keep the incisions dry for a week. The surgical glue will flake off and the sutures will dissolve in time - I need to be the incisions dry for a week.
I was curious and a bit anxious about my next infusion just 4 days after the the implantation surgery.  On check-in I said that i had a port installed on Monday.  I recognized the nurse who would be performing my first insertion.  She carefully organized a set of packets of items which would be required - including masks for both of us.  She prepared the area with sanitizer, brought over the access needle, asked me to take a deep breath and then applied the needle.  The prick was quick and certainly no worse than the arm poke typically done for lab work.  After flushes to ensure that the line was clear, blood for this today's lab work was drawn.  The access needle and catheter were left in place and secured with an adhesive patch - the connection would also be used to deliver the infusion.
We met with my doctor and then headed upstairs to the infusion suite.  My nurse was happy to hear that I had a port, and when my Keytruda was ready, the previously prepared line was connected.  No search for a patent IV vein!  When the infusion was complete, the line was again flushed and I was on my way.
I expect that at my next infusion in 3 weeks, the implantation incisions will be healed.  I may look into a getting a lidocain cream that some folks apply about an hour before the access needle is pushed in - but I am not sure that it's really necessary for me. 
As I am looking at continuing Keytruda for another year and a half - I believe that getting  the chemo port was a very good decision.

Despite the positive results I have seen with my treatment, I still hesitated before pressing the button to download the notes from today's CT scan with contrast and hesitated again to read through it.  Seeing the conclusion brought great relief and a prayer of thanks for God's continuing grace.

Since suspending my enfortumab vedotin (Padcev) - my peripheral neuropathy (numbness in fingers and toes) is subsiding, my sense of taste in normalizing and hair is returning. I am continuing to receive immunotherapy - pembrolizumab (Keytruda) once every 3 weeks.

I began infusions (Padcev+Keytruda on day 1,  Padcev on day 7 and repeat on day 21) in December.  I have three tubes of blood drawn before every treatment to get lab results which are reviewed before treatment.  On the last three visits, what used to be one stick to start the treatment IV has been turning into two misses - different locations on the left or right arm or hand.  The nurses then go in search of the most experienced person on the floor to put in the IV. I don't suffer from an abject fear of needles (tyrpanophobia), but I will say that I don't look when they are being put in.  However, I do feel like I am wearing out my veins and have scheduled an outpatient surgery procedure on  July 29 (before my next infusion on August 2) to put in a chemo port.  Folks I've asked ovewhelmingly agree with the choice.
 

On the day I departed to Chicago to attend my first annual ASCO meeting as a patient advocate (see previous post), I drew blood for a second circulating tumor DNA test.  Once again, no evidence of molecular, residual disease was detected.

After 6 cycles with both pharmaceuticals I began to experience low grade  peripheral neuropathy (numbness in fingers and toes) and dysgeusia (taste change).  We took a brief "holiday" with two cycles of Keytruda alone.  My adverse effects began to subside and my hair began to return.  I then had one cycle both at a reduced dose of Padcev. 
​
With a second negative ctDNA test and previous positve results reported in earlier posts - we agreed in consultation with my care team to suspend Padcev and maintain Keytruda.  We also agreed to continue to keep my bladder (no radical cystectomy or chemo-radiation) and monitor status with periodic ctDNA and imaging.

I am interested in collecting data from patients who have experienced a complete pathological response to Padcev+Keytruda treatment after TURBT (prior to radical cystectomy or chemo/radiation) to inform a safe dose de-escalation strategy.

I am also interested in gathering from any patients who have used fasting to avoid adverse effects with Padcev+Keytruda treatment.

I arranged to attend my first annual meeting of the American Society of Clinical Oncology as a new patient advocate.  With over 40,000 domestic and international specialists in each and all of the world's many cancers  in attendance (and over 800 advocates) - McCormick Place in Chicago is one of the few venues which could accomodate this event. [When leading software development for PET/CT I would attend the annual Radiological Society of North America meeting here after Thanksgiving every year.]
  
​I invested in this trip to meet and learn more of the role of patient advocates in supporting clinical research and cancer survivors and learn of the latest advances in the patient care and treatment of bladder cancer. I was encouraged the skill, knowledge, passion and compassion exhibited by the presentations and posters and plenary talks.

In the exhibitor hall I met with representatives of the manufacturers of my treatment - Astellas (Enfortumab Vedotin/Padcev) and Merck (Pembrolizumab/Keytruda) and maker of my circulating tumor DNA test (Signatera from Natera) for detection of molecular residual disease.  One my interests is dose de-escalation for patients with locally advanced/metastatic muscle invasive bladder cancer who exhibit a complete pathological response to this new treatment (~29% of patients in the EV 302 trial which led to FDA approval).  This is clearly a next question of great interest which may be addressed as EV 302 trial participatns continue to be followed and experience from folks like myself can be acquired.

Towards the end of the meeting, I attended a session "The Art and Science of Hope" and commented on the content and quality of this gathering.

I set out on one of my beautiful rural road bike routes on the early evening of Monday April 22.  The next memory I have is waking up in the Emergency Department of the University of Tennessee Medical Center- from which I pieced together how I arrived there.
I ride with my cell phone and use the Beacon feature of the Strava app which allows my wife to follow my progress on her phone - which stopped about half way through.  She called my phone and reached a very  kind Good Samaritan (actually one of at least two) who found me unconscious by the side of the road and called the police who in turn called an ambulance.

The police report indicates that I stated that I fell off my bike on West Bull Run Valley but could not describe why.  I'm told I was repeating myself a bit.  I was happy to see that the UTMC documents at least referred to a " very pleasant 67-year-old male" and "a good historian". 
I had a series of physical and mental examinations which yieled no remarkable suprises to attend to.  At 10 PM a CT's of neck, chest adbomen and pelvis were unremarkable - however CT of the head revealed:
      Subarchnoid hemorrage
      Subdural hematoma
in addition to face lacerations and scraping of the hands and side.  I was scheduled for a follow up at 4 AM to see if my situation would stabilize and allow me to be discharged.
On return to my room - my wife and I settled down to a long series of "Murder She Wrote" episodes on my TV.  I was then wheeled in for a second CT without contrast:

I was then discharged and Kathy drove us home.  I had a bit a room-spinning when rising from sleep which is subsiding.  My wounds are scabbing over.  Soon I'll bring my bike in for a once over and see if I'm ready to get back in the saddle.

In January I drew blood for a new molecular residual disease test - Signatera . The test detects circulating tumor DNA.   The first results take about 8 weeks because genetic analysis of your tumor is needed to inform the analysis.  The predictive power for treatment response appears quite impressive.
I was informed today that my test results are negative - which combined with the news from the previous post would indicate that my first line treatment is working very well.
I am scheduled to begin a 6th cycle of treatment (Keytruda/Padcevv) next Friday and will discuss next steps with my medical oncologist.
In addition to hair loss, I've started to have a runny nose and a bit of taste change.  Claritin did a fine job of clearing up the runny nose.

On March 6, 2024 I had a first PET/CT follow-up after 4 cycles of treatment with a combination of Keytruda and Padcev.  It took a bit of courage to press the button on my patient portal to bring up the radiology report which was available the next day.  My first PET/CT on November 11, 2023 showed very active pelvic  lymph nodes and changed my staging up to Stage 3 or 4 disease.
The news couldn't have been much better - the lymph nodes were no longer showing evidence of disease and there was no evidence of further spread.  As noted in the previous post when I had surgery in January no evidence of recurrence of the primary tumor was seen inside the bladder.

I attribute this to God's grace:
By the skills and persistence of those who developed my cancer treatment.
By those who participated in clinical trials to motivate accelerated approval of this treatment by the FDA.
By Medicare which allows me to afford and take advantage of this treatment
By my care team at the University of Tennesse Cancer Institute who arranged for and guide my treatment.
By my fasting regimen which I believe minimized adverse effects of treatment and may have contributed to treatment efficacy.
By the privilege to participate in the development of PET/CT at CTI/Siemens which found and monitors the presence of my cancer.
By prayers offered for me by so many family and friends and my church family.

I will continue treatment to see if my response is durable.  In January I gave a blood sample to run a new test - Signatera.  The first test uses DNA from resected tumor to inform bloold analysis which detects circulating tumor DNA to identify if there is any molecular evidence of residual disease.  This will complement my next follow up PET/CT.

 I was introduced to the health benefits of intermittent and periodic extended fasting and green exercsise during my health journey to reverse type 2 diabetes (see earlier posts).  While developing a proton therapy system I learned that fasting and exercise can reduce the adverse effects of radiation and chemotherapy  for cancer.

One component of my therapy is Padcev (see previous entry) - which delivers a cancer killing agent MMAE to cells (like my cancer cells) which express a protein Nectin 4.  Some studies have suggested that fasting may enhance the sensitivity of cancer cells to stress, while protecting normal cells from stress. This phenomenon is called differential stress sensitization (DSS). Fasting may induce DSS by lowering the levels of growth factors and hormones, such as insulin and IGF-1, that promote the survival and proliferation of cancer cells. Fasting may also induce DSS by activating a process called autophagy, where the cells recycle their damaged or unwanted components. Autophagy may help normal cells to cope with stress and remove toxic substances, while cancer cells may fail to perform autophagy properly and accumulate more damage.

The other component of my therapy is Keytruda (see previous entry) which boosts my immune response.  Studies have suggested that fasting may enhance the efficacy of cancer immunotherapy by boosting the immune system, increasing the immunogenicity of the tumor, and alleviating the immunosuppression caused the the tumor or chemotherapy.

I found green exercise - in my case e-biking on local roads - in addition to reducing stress and improving mode was also help in reducing insulin resistance and inflammation.  It may also boost the immune system and also enhance the effectiveness of chemotherapy and immunotherapy.

My regimen:
I begin fasting 2 days before my infusion, fast on the day of infusion and 2 days after.  The extended fasting induces autophagy.  The clearance half time for the cancer killing component of Padcev (MMAE) is 2.4 days. Fasting 2 days after infusion maintains maximal protection of normal cells and stress on cancer cells while the chemotherapy agent is most active.

I then keep my carbohydrate consumption low enough to maintain nutritional ketosis between infusions.  This helps to minimize the fuel source used by cancer low.

I continue to ride my e-bike at least 2-3 times a week which, as always is a great for stress relief, mood elevation and glucose control.

Results so far:
Other than losing a fair bit of hair, I have had no adverse effects from treatment.
I had surgery in January to remove a stent placed in my right ureter during a procedure to resect my primary tumor.  No evidence of the primary tumor was seen and my right kidney function was brisk so the stent was not replaced.

I am in my third cycle of treatment and on completion of the fourth I will have another PET/CT exam which will show whether treatment has been effective.

I would like to see more clinical trials designed to demonstrate and assess the benefits of fasting and exercise in cancer treatment and will be seeking opportunities to participate in such work.

References:

​Fasting and cancer: Benefits and effects
Adding fasting-mimicking diet to first-line carboplatin-based chemotherapy is associated with better overall survival in advanced triple-negative breast cancer patients: A subanalysis of the NCT03340935 trial
Short-Term Fasting Synergizes with Solid Cancer Therapy by Boosting Anti-tumor immunity
A review of fasting effects on the response of cancer to chemotherapy
Fasting and Exercise in Oncology: Potential Synergism of Combined Interventions
Researchers Look to Fasting as a Next Step in Cancer Treatment
Effect of fasting on cancer: A narrative review of scientific evidence​
Fast-Mimicking Diet is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer
​Safety and Feasibility of Fasting-Mimicking Diet and Effects on Nutritional Status and Circulating Metabolic and Inflammatory Factors in Cancer Patients Undergoing Active Treatment