Gladys was a test pilot. Her flight plan helped her live almost a decade longer than what was expected based on her diagnosis. Here is her story:
Gladys was diagnosed with a stage 3 endometrial cancer in 2007 at the age of sixty. Endometrial cancer is a cancer originating in the lining of the uterus. Her cancer was thought to be localized. She underwent a hopeful curative surgery. Radiation was then prescribed to improve her chance of local control and cure. She was zapped twenty-five times over five weeks. Things looked good for her.
For a couple of years thereafter Gladys was monitored with blood work and imaging. Sadly in 2010, her cancer cells came out of hiding to grow in her lungs, bones, and lymph nodes. With this documented growth, her cancer stage changed to stage four. There was no longer a chance of cure. Her cancer was going to kill her unless she died of something else. The something else would have to work quickly if it were to beat out her cancer though. The average length of life for a woman diagnosed with stage four endometrial cancer is twelve to fifteen months.
Gladys tried standard chemotherapy to treat her cancer and prolong her life. It worked for a little while but soon enough, her cancer grew and spread further in her lungs and bones. Her medical oncologist did not have another great treatment option. Gladys was referred to our phase one clinical trials team to consider participating in one of our available studies. I met her for this purpose in the summer of 2011.
Phase one clinical trials are specialized studies that test the safety of new drugs or drug combinations. There are few cancer centres with phase one trial capabilities – in part because of their infrastructure requirements, in part due to the expert knowledge necessary to run these trials safely and effectively. Most doctors who run these trials have extra fellowship training. I spent two years in the United States specifically for this reason before coming back home to Canada to use the skills I learned.
There are a number of different types of phase one trials. Some use a single drug that has never been given to people before; these are called “first in human” studies. Some combine drugs, often a new drug added to an older, more established drug. Some help determine if a drug or drug combination is safe in patients whose liver or kidneys are not working properly. No matter the type of phase one trial, the scientific reasons for doing these trials are to: 1) determine the correct dose of the drug or drug combinations to be used in people, 2) collect information on side effects experienced by patients, 3) determine what the drug is doing in the body, 4) determine what the body is doing to the drug, and 5) get a sense of what types of cancers are controlled by the drug or drug combinations.
Though there are exceptions, phase one studies are generally reserved for cancer patients whose cancer has no known therapy or for those who have exhausted all available standard treatments. My phase one practice is full of “the best of the worst” patients, meaning their cancer is growing with nothing left to try but they are still well enough to receive treatment. These trials are not for everyone – patients must be in decent shape; their blood work parameters must be mostly normal; there is a significant time commitment; and there are waitlists that cannot be avoided.
It is very important to say these studies are tightly regulated. We use drugs or drug combinations that have little to no evidence of efficacy. I cannot tell any of my phase one patients that these new drugs will work. Even if they do work, I cannot say they will be without significant side effects. We do not have a lot of data for the drugs I prescribe in these trials. Considering this reality, the primary concern of the doctors and nurses that oversee these studies is the safety of participating patients. Regulatory agencies, such as Health Canada and the Food and Drug Administration of the United States, strictly govern these trials. There are inclusion and exclusion criteria which must be adhered to. Enrolment in phase one clinical trials is limited in number and timing. Each group of patients receive a predetermined dose of the drug and are then observed for one or more treatment cycle before the next group of patients is permitted to enroll. Enrolment can only continue as long as there are no safety concerns. Each study has unbreakable rules regarding when we can treat a patient, when we cannot, and when we must remove a patient from trial.
The importance of phase one trials cannot be overstated. They are the first step in finding new and better cancer treatments. More notably though is that cancer drug development depends on the patients who are courageous enough to participate in these early trials. When I explain these trials to my patients, they sometimes comment that they are guinea pigs. I offer an alternative comparison by telling them they are test pilots.
When Gladys and I met, she was in relatively good shape. Her cancer was growing but she had limited cancer-related symptoms. She agreed to participate in one of our trials using a combination of traditional chemotherapy and a targeted oral drug that blocked several cancer growth pathways, including cancer blood vessel formation. While on this treatment, her cancer remained stable. She had side effects that required dose reductions – fatigue, mouth sores, and diarrhea – but she endured these well until her cancer decided to grow eight months in. Eight months was a remarkable amount of time to be on a new drug. Gladys had found the miracle of flight!
A few months after she came off her first study, Gladys decided to enroll in a second phase one trial. This second study drug was delivered to cancer cells by attaching a little beacon to the drug targeting a protein prevalent in certain cancer types, including endometrial cancer. Gladys only got a few doses of this fancy new drug. Near disaster occurred with some expected, and some unexpected, side effects attributable to the investigational drug.
Gladys developed sepsis, a bad blood infection, likely originating from bacteria in her bladder. The infection caused confusion, dehydration, and kidney damage. Admitted to hospital, she progressively worsened with increasing shortness of breath. Her lungs were struggling. She was diagnosed with a pulmonary embolism (blood clot in the lung). She was so ill she found herself in a step-down intensive care unit. There was question as to whether she would die from her side effects. Somehow, she rallied.
After this ordeal, it took Gladys several months to fully recover. Gladys told me she remembered nothing from her time in hospital. A CT miraculously showed her cancer had a magnificent response to the few received doses of clinical trial drug. All areas of cancer had shrunk. Only Gladys could tell us if all the toxicity was worth the benefit in controlling her cancer. She wasn’t sure despite the fact that she was confidently flying her plane with purpose, through a sprinkle of turbulence, right into the stunning sunset.
Amazingly, her cancer was mostly controlled without further treatment for the next two years. She had minimal cancer growth until the fall of 2014. By all accounts, Gladys should have been dead by then, but she had outwitted statistics. There is no doubt in my mind our trials weakened her cancer and helped her have more time with her family and friends.
Gladys was not finished flying. When she was ready, she soared even higher by participating in a third phase one study. She showed a giant thrust of faith by exposing herself to potential side effects again after her previous experience with the unknowns of our studies.
She flew on cruise control during her third trial. She may have even gone for a little nap! For the better part of two years, she remained on study medication taking treatment breaks here and there, mostly due to progressive fatigue, but she otherwise did well. In the end, Gladys landed her plane smoothly with hardly a bounce when we stopped her study drug because she just did not feel like she wanted to keep being bothered to come to the cancer centre.
Gladys struggled with bone related pain from cancer growth after that. Her tolerance for discomfort decreased. It was as if she had retired her worn-out wings which had eroded in the wind over so many years. She needed permission from her family and me to stay grounded from active treatment. She got it and I hope enjoyed the then fleeting time she had left without interferences of appointments and blood work and treatments.
Yes, Gladys was a test pilot. In fact, I believe Gladys was an ultimate fighter pilot. Only fifteen percent of women with metastatic endometrial cancer are alive five years after diagnosis. I do not know if there is a known percentage for how many women make it over nine years. I attribute the success Gladys had to her willingness to sit in a pilot seat – not once, not twice, but three times.
Thank you, Gladys, for 1) giving yourself a chance, and 2) giving of yourself so others might have a chance after you. You were such a brave woman for fighting the way you did. You were beautiful in flight. From my viewpoint, your flight plan was flown to perfection.
Author Notes:
I often get asked “why?”. Why did I get my cancer? Why is the chemotherapy not working? Why aren’t there other options for me? Why is it that millions of dollars are spent on research and development of cancer drugs every year and yet we still have people dying from their cancer?
There are not good answers to these questions. It’s true – millions of dollars are spent each year trying to find “the cure”. I wonder if cancer is just too complicated for that. Prostate cancer is different than breast cancer which is different than colon cancer and so on. A one-sized fits all cure is very unlikely.
I believe we do not have enough good drugs, or good enough drugs, for our cancer patients. There is no way to sugar coat this fact. Current data suggests less than ten percent of cancer drugs invented make it past clinical trial rigor to be approved for standard use – not the best statistic. Yet I can’t help but want to change the script on that and say it’s better than zero percent.
We must keep trying. Part of the reason I love my job is because of the hope that exists in clinical trials. I chose to specialize in clinical trials because I want to make a difference in the trajectory of cancer over my lifetime. Running clinical trials is one way I can make that difference. Each trial brings with it the chance of better outcomes for the patients I serve. There have been major gains in the treatment of many types of cancer over time and the breakthroughs keep coming. I am proud of this work by the oncology community.
My patients have more of an impact on the hope in clinical trials than I do. A patient might participate in a clinical trial because of some degree of altruism. I applaud this effort. But I hope their participation is both selfless and selfish. I want my patients to hope there can be mini-miracles in a clinical trial that will afford them an extra week or month or year with their loved ones. You never know when a drug will match up well with a cancer and hold it down for a three count the way Hulk Hogan often did with Randy “Macho Man” Savage. Hope is perhaps the most powerful engine of all.
I am curious to hear about a clinical trial you or your family member might have been involved with reader. Do you have a clinical trial story to inspire us? Whether successful or not, we can gain so much from asking: what did you learn from that experience?
