...the other half is surviving cancer treatment.
Even as I got the news that I was cancer free that spring, my bladder was not recovering from the surgeries and radiation as expected. In addition to side effects from Keytruda, I was experiencing what the doctors tactfully referred to as issues with “frequency” and “urgency.” There also were blood and, not infrequently, blood clots in my urine, as well as a few small instances of incontinence.
On top of these problems, I was beginning to get side effects from the Keytruda that was being administered in the clinical trial. An elaborate system exists to assure that study participants receive the right infusion while the information is kept hidden from the doctors and researchers involved in the clinical trial. The mystery was solved soon after my second infusion of the study drug when I started getting side effects described in the 22-page consent form. I thought it was good news that I was getting Keytruda instead of the placebo since that meant I had a chance to increase the odds of my long-term survival. But the short-term issues were far from pleasant. First was my thyroid response, an “uncommon” side effect experienced by 1% to 5% of patients taking Keytruda. The weekly blood test showed my thyroid gland had gone into hyperdrive and was overproducing. The next week I was hypothyroid, producing little or no thyroid hormone. My temperature regulation system was completely out of sync. I started to feel cold and wear sweaters or wrap myself in a blanket when the temperature in the house was over 70°, while at night I slept on top of the covers while Laura added an extra blanket.
The real challenge was to reduce the dose from 40 mg per day to 10 mg or less….More than 10 mg of prednisone a day would disqualify me from the clinical trial.
The thyroid issues were soon followed by a weekend of severe diarrhea, another “uncommon” side effect experienced by 1% to 5% of patients receiving Keytruda. Over-the-counter medications were ineffective, so I was prescribed 40 mg per day of prednisone, a strong steroid that brought things back under relative control in a few days. I joked that the use of steroids put my Olympic dreams on hold, but the real challenge was to reduce the dose from 40 mg per day to 10 mg or less in the 5 weeks before my next study drug infusion. More than 10 mg of prednisone a day would disqualify me from the clinical trial. I was ultimately on prednisone for over 3 months, which produced its own set of side effects. Skyrocketing glucose levels led to a referral to the Cancer Center’s endocrinologist, an expert in managing diabetes issues that are not uncommon in cancer patients. She put me on a program to wean me off prednisone and bring the blood sugar issues under control.
I was next referred to the Cancer Center’s gastroenterologist because the digestive issues persisted, though at a more manageable level. His task was to determine whether Keytruda was having a direct effect on my colon or was instead affecting the ability of my pancreas to produce enzymes essential to digestion, both side effects outlined in the clinical trial consent form. When a colonoscopy ruled out the possibility of non-Keytruda–related causes, he prescribed a drug (Creon) that substitutes for the pancreatic enzyme and directed me to take a pill before eating anything. If the digestive issues went away while on this regimen, it would mean they had been caused by a side effect of the Keytruda on the pancreas. Fortunately, the digestive issues went away before I had a chance to start on the Creon so we never determined the mechanism by which Keytruda was affecting my digestion. But the evidence was now clear: I was receiving Keytruda as part of the clinical trial.
The combined issues could be managed on a day-to-day basis but were particularly challenging during an 8-day trip to London and Scotland in May. “Frequency” and “urgency” can be difficult when in unfamiliar places, and my concern over Keytruda side effects was heightened because I received a Keytruda infusion the morning of our overnight flight to London. The side effects usually intensified in the days following an infusion. Although I did not feel fully comfortable doing this, I “played the cancer card” for the 7-hour flight back to the United States when I explained to the airline representative that an aisle seat was essential so I could reach the bathroom quickly if needed.
From Bad to Worse
The reasons behind the urinary issues were evident in a cystoscopy examination of my bladder in early July. It was done as part of regular surveillance that was set to take place every 3 months. The good news was that there was no sign of cancer in the bladder or the chest, abdominal, and torso CT scans taken per the clinical trial’s surveillance protocol. However, the inside of my bladder was inflamed, and there was “significant necrotic debris” (ie, dead tissue) that was “likely arising from the radiation treatment.” The doctor noted that one way to address my issues would be to remove the debris in another surgical procedure but suggested we wait and see if my bladder healed on its own.
Things went from bad to worse within a few weeks when I contracted the first in what turned out to be a series of urinary tract infections (UTIs). The problems with frequency and urgency increased, and suddenly I was incontinent at night, requiring the use of adult diapers. Having traveled to our second home in Vermont, I went to the local urgent care facility where the office test detected the presence of unspecified bacteria. As became the routine, I was prescribed an antibiotic, told that I would begin to feel better in 24 to 48 hours, and the urine sample was sent to a laboratory for further testing. Being conservative, I would schedule a game of tennis or golf in 5 to 6 days, only to be forced to cancel when the promised improvement did not occur. This routine repeated itself through the last 2 weeks of July and all of August as the UTI proved to be antibiotic resistant, with me alternating visits between the emergency room at Dartmouth Hitchcock Hospital and urgent care.
This was the low point in my cancer journey. I was miserable and in pain, and there was nothing surreal about it. The never-ending diet of antibiotics ruined my appetite and caused havoc on my digestive system. I lost 10 pounds over a 6-week period. To deal with the pain, I learned the secret to managing the recommended 6-hour intervals between doses of highstrength Tylenol and ibuprofen, which is to alternate between the 2 drugs every 3 hours. I couldn’t enjoy golf, tennis, hiking, and the outdoor wonders of Vermont—even driving 25 minutes to the grocery store was a challenge. It all came together in mid-August when I helped my son move from Long Island to Cleveland, Ohio. I joked that our 250-mile drive together from Vermont to Long Island and subsequent 2-vehicle 600-mile caravan to Cleveland qualified me to write a comprehensive new travel guide, Bathrooms of the Northeastern United States. The flights from Cleveland back to Vermont were equally challenging.
In consultation with the doctors, I decided in mid-August to have the surgery to remove the debris from my bladder. The hope was that with the debris removed the antibiotics would be able to reach and kill the bacteria that were “hiding out” in my bladder and causing the UTIs. The surgery could not come soon enough from my perspective. We returned to DC earlier than planned in the hope that I could get on the surgical calendar in less than the 3 to 4 weeks that was scheduled, but that was not to be. While at one level I understood how busy his surgical schedule must be, I was frustrated and angry at having to wait while in such discomfort.
A “Life-Threatening Event”
The surgery to remove the debris from my bladder, my fourth surgery in less than a year, took place on the morning of September 6. The surgery went well, and I was home that afternoon. Once again, there was no sign of cancer in my bladder. However, during the surgery the capacity of my bladder was measured as 100 ccs, about one-fourth that of a normal adult bladder. No wonder I was experiencing issues with frequency and urgency.
The infection that had tormented my urinary tract for the past 6 weeks was now a systemic infection…. blood tests showed that I was on the verge of acute kidney failure.
The next evening, I started to run a fever of over 101° and, following my post-op instructions, went to the emergency room at nearby Suburban Hospital. The infection that had tormented my urinary tract for the past 6 weeks was now a systemic infection. Equally troubling, blood tests showed that I was on the verge of acute kidney failure. The ER doctor started intravenous antibiotics and admitted me to the hospital.
The next 3 days were a blur as the doctors tried different antibiotics to control the infection and prevent severe sepsis or septic shock. I was receiving low doses of morphine for pain while my temperature spiked as high as 104° and kidney function worsened. According to Laura, I was at times confused, fell asleep in the middle of conversations, and, as we later learned, did not fully track what was going on or remember important discussions with the doctors.
As the infection worsened, the doctors diagnosed the problem to be a nonfunctional bladder that had become an obstruction. Urine was backing up from the bladder into the kidneys, causing them to become enlarged and infected. When tests showed that I was nearing total kidney failure, the decision was made to go around the obstruction by inserting tubes into my kidneys to collect the urine and divert it to collection bags outside my body. I never understood what an interventional radiologist did until one of them explained the nephrostomy tube procedure and had me sign the consent forms. Fifteen minutes later I was wheeled into a room with a body-sized imaging table and screen, sedated, and placed on my stomach as the doctors inserted first a wire and then tubes into the sides of my back and from there into my kidneys.
The procedure was a success. Over the next 2 days my temperature came down, the pain level eased, the infection started to clear up, and my kidney function began to recover. I left the hospital after 5 days with a new challenge: to learn to sleep, sit, and go about daily life with 2 tubes coming out of my back and urine collection bags at my sides. I would ultimately have them for 3 months.
A week later I had my regular appointment with the cancer doctors at Washington Hospital Center. Given recent events and the side effects I had experienced from Keytruda, we all agreed it was time for me to drop out of the clinical trial. I gained a new appreciation for how sick I had been when the doctor directed the research assistant on how to categorize my recent hospitalization for purposes of the clinical trial. It would be categorized as “a life-threatening event.”
« Read part 2 of David's story
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