Illustration by Colin Spence
In November 2008, Barrie Callaway and his wife, Coralie, headed to the Tom Baker Cancer Centre. Once there, he weighed in and went through a battery of tests – CT scans, bone scans, blood tests, the usual. At the end, his doctor gave him a prescription for a new drug – abiraterone – and sent him home.
Callaway, a retired teacher, had already lived with prostate cancer since 1998 and had been through numerous treatments. His first course of treatment was supposed to be a prostatectomy. But doctors discovered on the operating table that the cancer had spread to his lymph nodes. “In those days,” Callaway recalls, “they didn’t remove the prostate gland if they found that the cancer had spread.” So they stitched him up and in the intervening years he went through surgery, radiation and various types of hormone therapy and chemotherapy. His treatments in the past decade had suppressed the cancer for a few months at a time – even a couple years – but now his oncologist, Dr. Bernie Eigl, had little more to offer. Abiraterone was one of his last options.
Though people with prostate cancer can, like Callaway, live with the disease for years, in 2008 his PSA levels were doubling every six weeks, signalling advancing cancer. Prostate-specific antigen is a marker in the blood that helps doctors detect and monitor the cancer. PSA increases with age, but for a healthy 45-year-old, it’s generally below three and for a 75-year-old, below seven. Before he’d gone on the new drug regimen, Callaway’s PSA had rocketed to an alarming 39.7 points.
“I was scared,” Callaway says. “I was thinking, ‘What am I going to do? I’ve tried these hormone treatments and nothing’s working.’”
A month after starting abiraterone, he went back to the clinic for follow-up tests. “When I phoned up for results,” he recalls, “the nurse said that my PSA was 3.86.” He was pleasantly stunned with the new results: “I thought she’d missed a decimal point.”
There’s another story here. When Barrie Callaway checked into the Tom Baker Cancer Centre that November day two years ago, he was also checking in on his first day as a participant in a Phase III clinical trial. Discovered at the Institute of Cancer Research in London, England, the new drug abiraterone blocks an enzyme that plays a key role in producing testosterone, which drives the growth of prostate tumours.
The drug had gone through Phase I of clinical testing (when a handful of subjects try it to determine if there is clinical efficacy), and Phase II (when researchers study the effectiveness, dosage and safety of the drug on a particular form of cancer in a larger group). Now the drug was ready for Phase III, in which hundreds or possibly thousands of people would take the drug, with researchers comparing outcomes against those of standard treatment, looking also at side effects and costs. This is the last phase of the study before a drug can be produced and marketed.
In Alberta, there are currently more than 550 clinical trials for cancer treatment. Of that number, roughly 100 are open to accrual, which means that new patients can join after the study has started. “Clinical trials have become a standard of care, especially in oncology,” says Dr. Bernie Eigl, medical director of the Alberta Clinical Cancer Research Unit, funded by the Alberta Cancer Foundation.
“Trials are a vitally important part of improving care, survival and the quality of life for people with cancer.” Dr. Eigl says. “Prostate cancer is undergoing an exciting phase. We’re learning more about what pathways drive the cancer, and new drugs that have been designed to target those pathways are now in the late stages of clinical trial development.” There are new options for a disease that once had very few.
Trials can test the efficacy of hormone therapy, chemotherapy and immunotherapy, look at combinations of treatments and test new methods of surgery that are less invasive. They can take months or years and, if the trial is successful, patients sometimes continue on the therapy.
Such patient-based research is one of the most important areas of investigation into how to treat forms of cancer, and to learn how cancer progresses. In the abiraterone trial, for instance, scrutiny of the disease process meant doctors discovered that the cancer was mutating in a way they hadn’t seen before. This multi-level approach can lead to understanding how an illness functions and, hopefully, to lowering mortality rates.
Before each trial, researchers assess a patient to see if he or she qualifies. Health problems, such as other cancers or diseases, might disqualify a potential participant.
For patients, the next step is reviewing the risks. Dr. Eigl sent Callaway home with a lengthy contract to review. Patients are warned of the possibility that drug won’t work or that it will have side effects. For example, one man on Callaway’s study had an allergic reaction to the drug and had to withdraw. “It doesn’t matter to me if you choose the trial,” says Dr. Eigl, “but that I have treatment options to offer you.” Most trials offer some of the participants the trial drugs, while others receive standard therapy, which amounts to the current best standard of clinical care for their disease.
There are other benefits to participation. Trial subjects are tracked closely, and receive numerous and frequent blood tests, CTs and bone scans to see if and where cancer is spreading. Progression of the cancer might be noticed earlier. For others, however, a trial will produce no benefit and may harm, Dr. Eigl says. “The only person who will benefit from a trial for sure,” he says, “is the person who has cancer down the road.”
A trial can also buy time as researchers develop new treatments. The clinical trial of this new drug has slowed the progression of Callaway’s prostate cancer and his PSA levels today are 1.1 – a fraction of what they were two years ago. But patient and doctor are realistic. “Cancer mutates over time,” Dr. Eigl says. “At each stage the timeline shortens. It’s like a snowball rolling down a hill. The farther down it rolls, the faster it gets.”
Chipper and friendly, Callaway is a glass-half-full kind of guy who has approached his diagnosis and treatment with a positive attitude. He attends meetings for people with prostate cancer, and continues to enjoy retirement. “About five years ago it hit me: you know, there’s no cure for prostate cancer. You might go into remission for a long time, but there’s no cure.” He knows that someday the abiraterone will stop working and his PSA levels will creep up. “When abiraterone stops working for me,” he says, “I hope there’ll be another trial.”
In the meantime, he’s getting ready to go on another cruise: the Caribbean this time. He’ll head to the Tom Baker Cancer Centre for meds that will last him all 25 days of the trip. Life, he would tell you, goes on. In fact, he says that he and Coralie recently celebrated their 40th wedding anniversary. In the background, his wife corrects him: it was their 45th. “Oops. Well, I’m hoping to be around for the 50th anniversary.”
Debunking the Myths About Clinical Trials
Trials are difficult to find.
False. In Alberta, there are more than 150 studies recruiting subjects. Alberta Health Services’
www.alberta.canadiancancertrials.ca lets you search for potential trials based on factors such as the type of cancer and location of the trial. (You can sign up for email alerts about the latest trials). Find trials in other parts of Canada at www.canadiancancertrials.ca.
Patients on trials get a better quality of care.
False. “I often have patients who are sad because they didn’t qualify for a trial or we didn’t have a trial to offer them,” says Dr. Bernie Eigl. “It’s important for them to remember that a trial is unproven. They could have derived no benefit or they could have been harmed by participating.”
Placebos are rarely used.
True. Randomized trials often give half the study subjects their old treatments and half the new treatments.
There are many kinds of trials.
True. There are trials using everything from gene therapy (manipulating a gene to encourage the body to mount a defence against the cancer cells) to angiogenesis inhibitors (a drug that blocks the creation of new blood vessels to the tumour, effectively starving it).
Once a trial has started, it won’t take new patients.
False. Many trials are open to accrual, meaning they are still accumulating data and adding subjects.
Ready for a Trial?
1. Talk it up. Ask your doctor which studies might be right for you, and about risks and benefits. If you’re in the pre-symptom stage of cancer, standard treatment might be your first course.
2. Look around. Make your search easier with online trial finders. Search www.canadiancancertrials.ca for potential trials based on factors such as the type of cancer and location of the trial. Find trials in other parts of Canada at www.canadiancancertrials.ca.
3. Know thyself. What level of risk are you willing to take? A Phase I study, for instance, may have limited impact on your outcome, though it helps the research process. In some trials, two patients will receive the new drug and one will receive a placebo or traditional therapy. Studies have data safety monitoring boards and patients are closely monitored, but studies are inherently experimental.
4. Read the fine print. Once you’ve found and qualified for a trial, take the consent form home to review. Ask the trial doctors questions.
5. Plan your time. Studies frequently last several months and include monthly or bi-monthly visits to the clinic for CT and bone scans and other tests. Each study has a pre-determined schedule. A plus is that this means closer monitoring of your cancer. On the flip: you might feel like slave to the schedule.
6. Everything ends. The study is over, now what? Some trials, like those for prostate cancer, track patients for years and, if the drug is successful, trial subjects may continue on the treatment as long as it’s beneficial. If that treatment someday stops working, you can investigate other trials.