By Fadlo R. Khuri, MD, FACP
As a physician focused on the treatment of patients with cancer, many of whom face a potentially incurable disease, I make 3 promises to my patients:
1) We will always tell them the truth.
2) We will always do our very best for them, placing their interests and those of their families above all others.
3) We will never abandon them.
These are important words to relay to a patient, particularly those who are considering participating in clinical trials. The question, then, is, "Why should cancer patients participate in clinical trials?"
Cancer clinical trials are one of the most important methods we have to move the field forward. After all, it was through clinical trials that we have developed cures for childhood acute leukemia, Hodgkin disease, and testicular cancer, how we developed long-term highly effective therapies for chronic myeloid leukemia and breast cancer, and how we created personalized genetic therapies for lung cancer, melanoma, and other diseases. Cancer clinical trials also let us know how patients are feeling about their care, and can improve approaches for the treatment, prevention, and cancer screening tests for cancer patients.
One of the first things I do as the treating physician is to complete a history and physical exam of the patient. The information I gather helps me form an opinion, and it helps me gain the trust of the patient and his or her family.
After obtaining the history and physical information that I need, I discuss standards of care and explain why this care, like radiation or chemotherapy, might work (or not work). It is important to acknowledge our limits while reassuring patients of our considerable experience in treating others with a similar disease. I have occasionally seen physicians who rush to discuss the clinical trial before going through the full range of standard treatment options available. Identifying the standards of care and presenting them as a viable option for patients is far more likely to reassure patients that all options have been carefully considered.
Types of clinical trials
Next, I discuss possible clinical trials that the patient is eligible for. I usually start by explaining that different phases of clinical trials have different purposes. Phase I trials generally look to find out which dose of a drug or drug combination can be tolerated without debilitating side effects. When a typical phase I trial ends, we may have established a dose of a drug or combination but generally don't have enough information to decide whether this particular drug or combination may effectively work against a certain disease.
We usually consider Phase I trials with patients who have limited treatment options, including those patients who have already tried both conventional treatments and more promising - clinical trials. While I repeatedly say that the likelihood of benefit for patients, including cure, long-term remission, prolonged survival, or symptom relief, is in the range of 1% or less, recent studies from our group and others have shown that at least 70% of patients who participate in these early phase I or dose-finding trials do so because they believe they are likely to derive some benefit from this treatment, and because they want to help other patients who come after them. This speaks to a continuing gap between physicians and patients with regard to our ability to consistently communicate the purpose of these phase I trials. We want patients to participate in these trials, but we need to make sure they understand what the risks are and be realistic, but not pessimistic, about the chance that they will benefit from participating.
Phase II clinical trials test a drug, combination of drugs, or device that has or have shown some promise against a certain disease in humans. If it shows enough promise in phase II studies in humans, then a phase III (or "randomized") trial compares that drug, combination of drugs, or device to the usual standard of care for patients. In phase II or phase III trials, patients have a reasonable chance of benefit (cure, long-term remission, prolonged survival, or symptom relief); phase III trials are planned to show definitive benefit compared to the standard of treatment for patients with that disease.
When I'm discussing these clinical trials with my patients, I make sure to include the reason the investigators are conducting the trial, and the risks and benefits of participation. And I always, always reassure the patient that information we get from this clinical trial will be important for the development of new options for cancer patients. It is equally important to reassure them that their private and personal information will be fully protected, and that data from the clinical trial will be presented such that no patients' identities are revealed.
I next discuss the potential known side-effects of the agents involved in the trial, while also admitting that other side-effects may emerge during treatment. One of the worst things a physician can do is to allow a patient to participate in a clinical trial without fully understanding the potential side effects. One of my key goals is to ask the patient never to minimize their symptoms, to share with us their timing, severity, durability, and exact nature.
Be open, honest, and connected
A critical step here for the treating physician is to understand the reasons behind patient participation in clinical trials. In general, patients with cancer or blood diseases who participate in clinical trials do so because they believe trials are their best options to go into remission or to manage painful symptoms. Patients want to be kept informed as to whether they or other patients are benefiting. I and other doctors have embraced the practice of making sure patients know about the overall outcome of completed trials, and we invite and try to answer all their questions.
Informed patients who have participated in clinical research make powerful advisors and advocates for future participants. In fact, these patients are a vastly underused resource, and I have learned over the years to gratefully accept when patients volunteer to speak to others about their experience on a clinical trial or with a particular therapy. It is wise to keep in touch with as many patients as possible who have participated in our clinical trials, and most of us in the medical profession celebrate these patients on an annual basis.
To close our discussion, in keeping with the goal of cooperation and transparency, I then outline my opinion as to what the patient should do. This is an important part of modern medicine. All too often, with the swarms of federal regulations, personal injury lawyers, and other factors that weaken the modern physician-patient bond, physicians step back and present the treatment options as if part of a simple menu for patients to choose from. I disagree with this approach, believing that the physician and the healthcare team should play the crucial role of informing the patient why they believe that one course of treatment is the best choice. In the event that the patient chooses a different option -- and that is their right - they have received their doctor's best and most considered advice.
I reassure patients that no matter what their choice is, they will remain my patients and I will continue to keep my promises to them of truth, continued support, and optimal care. Knowing this is valuable for the patient and allows them to make their choice of whether or not to participate in a clinical trial in an atmosphere of mutual trust and respect. Most importantly, we want to get rid of any unrealistic fears the patient and family might have, and reassure them that they are being treated as people, not as the subjects of experiments, with their rights, feelings, and, yes, their best interests always foremost in our minds. After all, no physician should want to coerce a patient into participating in a cancer clinical trial. But with only 5% of all cancer patients who are eligible for clinical research studies participating in clinical trials, it is essential that patients and their families are aware of them and their benefits.
Taking time to go over all options, and then giving the patient your best judgment in an atmosphere of openness, candor, and mutual respect, builds the most sacred aspect of the bond between the patient and the physician, that of trust and shared decision-making. There is no more important aspect of the practice of medicine that I can think of.
Find more information about clinical trials, including the American Cancer Society Clinical Trials Matching Service.
Dr. Khuri is a practicing oncologist; professor and Roberto C. Goizueta Chair, Hematology and Medical Oncology; deputy director, Winship Cancer Institute, Emory University; and Editor-In Chief, CANCER.