The line between life and death is thin. Individuals can cross it in the time it takes for a muscle to contract, an eye to glance into space or a neuron to fire one final time. Don Devereux has stood at that mystery-shrouded line many times.
Sometimes it was his choice, sometimes it wasn’t. After he failed to secure a deferment on humanitarian grounds, Devereux, then 23, went to Vietnam in December 1969 to fight in the jungles there as a soldier in the 1st Infantry Division. After President Richard Nixon announced the division’s withdrawal from Vietnam in 1970, Devereux had the opportunity to complete his military obligation with an eight-month reassignment to the States in a non-combat role. He chose a riskier route, remaining in Vietnam for three more months to finish his tour.
Devereux returned to the States in one piece in February 1971, leaving behind the thickets and rice paddies of Southeast Asia for the California coast. He parlayed his accounting degree from San Jose State University to a job with spice manufacturer and distributor McCormick & Company, married, helped to raise two daughters and eventually settled in a house in Santa Cruz. He golfed, hiked and bicycled along the sun-splashed shorelines of central California, and skied regularly at Lake Tahoe.
And then, prostate cancer
But in January 2003, disease forced Devereux to again consider his mortality – and not for the last time. He was diagnosed with colon cancer, which led to surgery and 24 chemotherapy treatments. Two years later, he learned the cancer had spread to his liver; another surgery and 24 more chemotherapy treatments followed.
His chances of surviving two more years were slim, but Devereux defied the odds. He moved to Colorado in 2006 and was alive and kicking in 2012 when yet another blow arrived: a prostate cancer diagnosis. That led to surgery and 39 consecutive radiation treatments.
Sixteen years down this tortuous road, Devereux is still standing and determined to stay on the living side of the life-death line, one leg-lift and pedal-push at a time.
Prostate cancer and exercise
Devereux is the first patient enrolled at UCHealth University of Colorado Hospital in the multinational INTERVAL-GAP 4 study, sponsored by the Australian-based Movember Foundation. The trial targets patients like Devereux who have metastatic castrate-resistant prostate cancer. In these patients, the cancer spreads despite treatments to suppress their testosterone levels – the primary driver of the disease.
The study aims to determine if a carefully designed and tightly monitored regimen of high-intensity exercise can improve survival in these patients. That goal makes it unique, said Dr. Elizabeth Kessler, assistant professor in the Division of Medicine Medical Oncology at the University of Colorado School of Medicine and a genitourinary cancer specialist who practices at the UCHealth Tony Grampsas Urologic Cancer Clinic on the UCHealth Anschutz Medical Campus. Kessler is co-principal investigator for the INTERVAL study in Colorado with Dr. Kathy Jankowski, an exercise physiologist and associate professor with the University of Colorado College of Nursing.
“Many other studies looking at exercise have evaluated post-treatment delay of cancer recurrence or its effects on quality of life or fatigue. Some have evaluated reduction of morbidities, like surgery,” Kessler said. “This study looks directly at the question of ‘Does exercise help people with cancer live longer?’ It’s an important and complicated question.”
Jankowski, who works with patients in tandem with other exercise physiologists in the School of Medicine’s Exercise Research Lab, said the study intrigued her, in part because it focuses on men weakened and in pain because of the spread of the disease, especially to their bones.
“This trial is specifically for men who have metastatic cancer and have had failed therapy for it,” Jankowski said. “This is a population that is typically excluded from exercise trials because of the risk, but this trial was designed for them. It’s a new frontier.”
Active resistance to cancer
At the start of the first year, which Devereux recently completed, participants enrolled in the exercise group – a control group gets only psychosocial support – work with an exercise physiologist three times a week on a “periodized” regimen of stationary bike and weight-lifting work, an approach used by many athletes, Jankowski said.
“It means that the intensity and duration of the exercise increases and decreases and fluctuates over weeks and months,” Jankowski said. “That keeps it fresh and allows the musculoskeletal and cardiorespiratory systems to adapt to the training.”
Patients also work at home, completing one weekly 40-minute round of cycling on a stationary bike, she added. After nine months, they move to two weekly sessions on their own; in the second year, they come in for supervised training just one time a month, with the expectation that they will continue to train regularly at their homes or a local recreation center.
“It’s important that they become self-reliant and carry the exercise over to their daily lives,” Jankowski said.
Safety first
The study’s broad exercise framework includes careful attention to the needs and safety of each patient, each of whom receives regular bone scans, blood and urine draws and other tests and an exercise plan prescribed through the study’s central site for his specific medical condition.
“The study is quite thoughtful in its design in that the exercise is tailored around the sites of the metastatic disease,” Kessler said. “It tries to meet people where they are.”
For example, Devereux’s prostate cancer has invaded the bones of his shoulders, sacroiliac joint, and pelvic crest, as well as several joints of his thoracic spine. To avoid stressing and possibly fracturing those bones, he concentrates on leg lifts and curls, as well as his stationary bike work.
Medication assistance
Devereux said the regular work with the exercise trainers at UCH and self-directed sessions at recreation centers near his home in Gilpin County and in Washington Park during visits with a lady friend have helped to restore strength in his calves and thighs. He’s also benefited greatly from treatment with the oral medication Zytiga, which helps to block the production of testosterone and other hormones from the testes, adrenal glands and cancerous tumors themselves.
The Zytiga therapy, supervised by Dr. Thomas Flaig, a UCHealth medical oncologist, urologic cancer specialist and associate dean of clinical research at the CU School of Medicine, has tamed Devereux’s previously soaring prostate specific antigen (PSA) numbers. But the side effects of hormone-blocking treatments can be daunting: hot flashes intense enough to fog up his sunglasses; “immense” muscle loss; weight gain; and lethargy, Devereux said.
When Flaig mentioned to him the possibility of enrolling in the INTERVAL trial, Devereux jumped at the chance.
“I wanted to do more exercise to offset the side effects of treatment,” he said. “It has done that very well.”
The hot flashes have tapered off, Devereux added, even as his motivation to confront his disease has taken off. “[The exercise] got me up and going, gave me new strength and animation. My life and days are more full than they were beforehand,” he said.
Emotional fallout
Devereux estimated that his commitment to the study regimen, with direction and encouragement from the exercise physiologists, has helped him improve his 40-minute bike-ride distance and leg extension and curl strength about 50 percent each. But he added that the work is part of a larger tapestry that includes the Zytiga therapy, care from Flaig, renewed social connections and a general refusal to surrender to the solitude of disease.
Living in a home above 9,000 feet with a view of Mount Evans and easy access to the Arapaho and Roosevelt national forests for snowshoeing was for many years a great source of strength, Devereux said. But his prostate cancer diagnosis dimmed his view.
“Solitude turned to depression,” he said. “I was nowhere near as positive a person as I had always been known. I felt like my days were numbered. Now I’m much more outgoing. I’m getting back to doing more walking and hiking and I hope to get back to golfing.”
Quality concerns
His experience underscores a key secondary outcome the INTERVAL trial researchers want to measure: improvements in quality of life. It’s a question that keenly interests both Kessler and Jankowski.
Kessler, for example, focuses much of her research and clinical practice on finding the most effective ways to support patients with cancer. That includes reducing pain, managing fatigue, improving sleep and stabilizing mood.
“Inevitably, however, much of cancer research ends up being boiled down to this aspect of ‘did we help people living longer?’” she said. “Is that the right question to ask? I’m not sure. Should we be exploring others? Definitely. We may find that the primary outcome of this study is not achieved, that exercise does not improve overall survival. However, it may improve patients’ lives in so many other ways that it’s still something we look at as beneficial.”
Jankowski, who spent years in clinical research with CU’s Division of Geriatric Medicine, noted that in geriatrics, “health span” is distinguished from “life span” – the latter being how long one lives; the former being the number of healthy years one lives.
“Our goal is to add high-quality time to one’s life,” Jankowski said. “There are well-being standards in this trial, and we hope to learn more about the effects of exercise on health quality in this patient population.”
For his part, Devereux said he’s not worried about handling the exercise regimen on his own. He’s made it part of his improbable battle against disease. The guy who figured he had a couple of years left after being diagnosed with liver cancer in 2005 continues to not only lengthen his life but find ways to improve it.
“I’m living on borrowed time,” Devereux said. “I consider every day a new day and a blessing.”
To learn more about the INTERVAL trial, contact Dr. Elizabeth Kessler at [email protected].