The following excerpt is taken from Chapter 1 of Cancer Clinical
Trials: Experimental Treatments & How They Can Help You by Robert
Finn, copyright 1999, published by O'Reilly & Associates, Inc. For book
orders/information, call (800) 998-9938. Permission is granted to
print and distribute this excerpt for noncommercial use as long as the
above source is included. The information in this article is meant to
educate and should not be used as an alternative for professional
If you or a family member has been diagnosed with cancer, you probably have many questions and want to make sure you are making the best possible decisions for treatment.
Real promise in new treatments
Although cancer continues to be a frightening disease, cancer research now offers genuine hope for better cures. Basic research on cell biology is finally yielding important clues about the nature of cancer, and these clues are leading directly to promising new treatments. Physicians are finding better ways to alleviate cancer pain and some of the toxic side effects of chemotherapy. Medical device companies are testing new ways to detect cancer in ever earlier stages. And researchers are even creating therapies that will prevent the development of cancer in people who are at risk.
None of these new developments leap from the scientist's mind to the clinic in a single step. The brightest of bright ideas have to be tested in the laboratory, first in the test tube and then on animal models of cancer. Only if these preliminary tests give some evidence that the new treatment works and is reasonably safe is it tried on human beings--in a clinical trial.
Clinical trials of new therapies--and the hope they bring--are important, because cancer statistics are stark and unpleasant. According to the American Cancer Society (ACS) and the National Cancer Institute (NCI), cancer is the second leading cause of death in the United States, exceeded only by heart disease. In 1998, there were an estimated 564,800 deaths from cancer, fully one-quarter of all the deaths in the US. More than 1.2 million Americans were newly diagnosed with cancer in 1998, and a total of 8 million living Americans have a history of cancer.
In the 1930s only 25 percent of cancer patients survived five years. The five-year survival rate rose to 40 percent in the 1990s, but much of that modest improvement may be due not to better treatment but to the fact that we're able to detect cancer much earlier these days. Earlier detection means a longer period of survival after diagnosis, even if the course of the disease remains exactly the same.
Despite decades of intensive research, despite the War on Cancer declared by President Richard Nixon in 1971, and despite generous funding, dedicated investigators, and courageous patients, improvements in cancer treatment have only been incremental, and cures remain elusive. One thing is certain, though: every potential new therapy must pass the rigorous test of clinical trials before it can come into wide usage.
What is a clinical trial?
New treatments aren't tried casually or haphazardly. Legitimate researchers don't say, "I'm really excited about my laboratory results with Compound X. Joe Smith here has cancer. Let's see if it'll cure him!" Hundreds of years of experience with the scientific method have taught researchers that in order to learn something about the physical world, you have to ask precise, very narrow questions, you have to design an experiment that will give you an unambiguous answer to those questions, and then you have to run that experiment carefully, so it genuinely answers the questions you're asking. When the subjects of the experiments are human beings, there are also important practical and ethical considerations that must be taken into account.
Experiments that are conducted on human beings, and that are intended to answer a therapeutic question, are called clinical trials. There are essentially three types of questions that investigators must answer, in order, in clinical trials:
New treatments reach the general public only if all three of those questions can be answered affirmatively.
- Is the new treatment safe?
- Is the new treatment effective?
- Is the new treatment better than other treatments?
If all human beings were the same, you could get away with conducting those experiments on just a handful of people, and you'd have your answer in short order. Give Mary a dose of Compound X. If she doesn't get sick, it's safe. Give Alice several doses. If her cancer goes away, it's effective. Give Sam Compound X and give Jim the current standard treatment. If Sam does better than Jim, Compound X is better than the standard treatment.
Unfortunately, human beings are complex biological organisms, and cancer is a puzzling and often perverse disease. A certain drug might make some people very sick, while others tolerate it well. Cancers sometimes go away spontaneously, even without any treatment at all. Drugs that work extremely well in destroying one person's cancer may have no effect on another person.
The only way to get reliable answers to the questions that are asked in clinical trials is to try the new treatment on hundreds or thousands of people. If most people don't get sick, it's safe. If it makes most people's cancer go away, it's effective. If on average people do better with Compound X than with the standard treatment, then Compound X is better. This is an extremely expensive and lengthy process that costs hundreds of millions of dollars and can take many years. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), it takes on average 15 years to bring an experimental drug out of the lab.
Why clinical trials take so long
Everyone wishes drug approvals could move along much more swiftly. If they did, ineffective treatments could be discarded and effective treatments would reach people with cancer sooner.
Some of the factors that retard progress are administrative. The US Food and Drug Administration (FDA) has developed a complex, lengthy, and expensive process that pharmaceutical companies must follow before new drugs are approved for sale. Although this process is intended to keep unsafe and ineffective drugs off the market, many activists charge that the FDA's regulations have the effect of keeping lifesaving treatments away from the people who need them most.
In response to these criticisms, in 1996 the FDA made it easier to demonstrate a new treatment's effectiveness. Before the new rules went into effect, pharmaceutical companies had to demonstrate an actual increase in survival time for a cancer treatment to be considered effective. The new rules allow researchers to use "surrogate markers"--such as tumor shrinkage--as a somewhat more indirect indication of effectiveness. This is expected to speed up the drug approval process significantly.
The FDA's rules are not the only reason that it takes so long to evaluate a potential cancer treatment. According to the NCI, fewer than 5 percent of adult cancer patients ever participate in a clinical trial. According to some estimates, if just twice the number of cancer patients could be persuaded to participate, new treatments could be evaluated in half the time it takes now.
There are many factors holding down the number of clinical trial participants, and it's unclear which are the most significant. Among them, in no particular order, are:
- Lack of awareness. Some cancer patients may not be aware that clinical trials are an option.
- Reluctance to second-guess the physician. Some cancer patients may fear that asking their physicians about clinical trials would be perceived as a criticism of the treatment they're receiving.
- Unreceptive physicians. Some physicians--amazingly, even some oncologists--express distaste for clinical trials. Recalls cancer survivor Gary Schine, "When I mentioned clinical trials, my doctor told me, 'I don't want my patients being treated like guinea pigs.'"
- Reluctance to refer. Some physicians may be hesitant to refer their patients to clinical trials at other institutions. And even when they are willing to suggest a clinical trial, they may only suggest trials that they are personally involved in.
- Overly strict eligibility requirements. Some clinical trial protocols allow investigators to enroll only patients with specific medical histories. Some critics of the current system believe that there are good reasons to broaden inclusion and exclusion criteria, allowing more patients to participate.
- Difficulty finding clinical trials. Many patients--and sometimes even their physicians--don't know where to go to find lists of clinical trials for which they're eligible. Fortunately, the search is much simpler now than it used to be. A toll-free phone call to the NCI's Cancer Information Service or a check of sites on the Internet can yield good lists of clinical trials targeted to your condition.
- No clinical trials available. For some types of cancer, or for some people with certain medical histories, there may be no clinical trials currently being conducted. New trials are announced continually, however, and if you want to participate in a clinical trial, it's worthwhile repeating your search on a weekly or monthly basis.
- Distance from major medical centers. Many patients don't live near major academic medical centers, where most clinical trials are conducted. In response, the NCI developed the Community Clinical Oncology Program (CCOP) that can often allow an oncologist far from a major medical center to administer experimental treatments locally. But some oncologists aren't hooked into CCOP, and some trials can only be conducted at certain central locations, necessitating the difficulty and expense of travel.
- Difficulty with insurance coverage. Many insurance companies and health maintenance organizations (HMOs) refuse to pay for experimental treatments, or even for routine care when experimental medications are free.
- Other financial burdens. Some trials may involve extra clinic visits, and these can result in lost wages or child-care costs.
- Poor explanation of disease or prognosis. If you're not given honest information about how serious your disease is and how effective or ineffective current standard treatments are, you may be unlikely to consider clinical trials.
- A good prognosis. If you have a type of cancer that is almost always cured by the standard treatment, there will be little reason for you to consider a clinical trial.
- A desire to stop fighting. Some people with cancer make a rational decision to stop treatments and to accept disease progression. There are, however, some clinical trials--such as those of new treatments for cancer pain--that may be appropriate even if you are in that situation.
- Reluctance to be randomized or to receive a placebo. Many people fear that if they enroll in a clinical trial they may be assigned randomly to receive less effective or inactive medication.
- Fear of side effects. New treatments have unknown side effects, and learning about these is one of the main aims of clinical trials. But as Gary Schine likes to point out, "In this country far more people have been helped than hurt by clinical trials."
Should you consider a clinical trial?
There may be many reasons not to participate in clinical trials, but there are also plenty of reasons to seek them out. You will have the opportunity to get a new treatment years before it's available to the general public. While it clearly won't be a proven treatment, it will be one that knowledgeable physicians regard as promising. While you're in the clinical trial, you'll most likely benefit from an especially high level of medical care. And even if the treatment does not help you personally, you can take comfort in the fact that your participation will help other people with cancer down the road. Medical science cannot advance without the altruism of clinical trial participants.
Please note that we do not urge everyone with cancer to participate in clinical trials. Many of the reasons not to participate are valid, and the decision to participate in a clinical trial is a personal one. If you have cancer, you must make that decision yourself, in consultation with friends, relatives, physicians, and spiritual advisors. It's a decision that depends on many factors, which are thoroughly explored throughout this book.
It is the opinion of many medical professionals, that if you have cancer, you should at least consider the available clinical trials, along with all your other treatment options. If you are not evaluating potential experimental treatments alongside the standard treatment protocols, you're simply making a decision without access to all the facts.
Some physicians, such as Dr. David Jablons, a thoracic surgeon at the University of California, San Francisco, express an even stronger point of view:
I think that all patients with cancer should be in a clinical trial. If they're not in a clinical trial, it implies that we know how to treat the disease, which for all but a few cancers, we don't.
Thankfully, there are a few cancers for which the standard treatments are highly successful. Caught early, many skin cancers can be removed completely before they spread, for example. This illustrates how critical it is to get honest information about your prognosis--a forecast of the course of your disease and an estimate of your chance for recovery--from your doctor. Lydia Cunningham Rising, a patient advocate, observes:
The worse your prognosis is, the more you should consider a clinical trial. But some doctors don't like to quote statistics. I understand they don't want to make the patient feel like a statistic, but if you do not know that you have a cancer with a 2 percent five-year survival rate, you aren't really going to think about clinical trials. When that is hidden, doctors are taking away the patient's ability to decide what to do.
If you can't get a straight answer from your doctor, an American Cancer Society sponsored book written by Gerald P. Murphy, MD, Lois B. Morris, and Dianne Lange called Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery (Viking Penguin Books, 1997) is an excellent source of information on specific cancers, their standard treatments, and their likely outcomes. It's available in many libraries and bookstores.
Although a poor prognosis increases the chance that you'll want to consider clinical trials, it doesn't necessarily follow that you should ignore this option if your prognosis is good. There are clinical trials of adjuvant therapies that are focused on preventing recurrence of disease. There are prevention studies. There are studies focused on alleviating the side effects of other therapies. Clinical trials are not only an end-of-life option, and anyone with a diagnosis of cancer should at least consider clinical trials.
Traditional and alternative medicine
Many doctors have a strong bias in favor of what is typically called traditional or conventional medicine. Those adjectives are misnomers, however. Modern medicine is anything but traditional or conventional.
Modern medicine depends on the scientific method, which is certainly one of the crowning glories of human thought. The scientific method gives us an extremely efficient way of asking precise questions about how nature works, and (wielded correctly) it yields precise answers. Using the scientific method, modern medicine has rapidly made great strides in treating individual illnesses and in improving general human welfare.
In fact it is alternative medicine that tends to be far more tradition bound. Many advocates of alternative medicine point proudly to the fact that their chosen methodologies have been practiced for hundreds or thousands of years, and contain the wisdom of the ancients. Now that's traditional. Of course, the ancients believed that many physical illnesses could be treated by draining people of their excess blood. And they believed that people who were mentally ill should have holes cut into their skulls, to let the demons escape. Clearly, some of the ancients weren't all that wise.
This is certainly not to say that all alternative medicine is worthless. On the contrary, many of modern medicine's greatest successes rest on traditional foundations. The ancient Greeks used a form of aspirin contained in willow bark to alleviate pain. Digitalis, which increases the contraction of the heart in congestive heart failure, is derived from the foxglove plant, and was used by generations of women healers in England. Curare, an important drug used for muscle relaxation during anesthesia, was discovered by studying the poisoned arrows of South American hunters. There's an entire branch of science called ethnopharmacology, whose goal is to study traditional remedies in the search for new medicines for modern-day ailments.
This is also not to suggest that people with cancer should avoid alternative medicine. First of all, there are clinical trials of various alternative medicines underway, and people should consider participating in them. It's only through such clinical trials that the alternatives can be proven safe and effective--and incorporated into the mainstream--or proven unsafe or ineffective, and discarded.
Secondly, even alternative methods that are unproven may have beneficial effects. For example, there may not be any studies proving that quiet meditation is an effective cancer treatment. However, meditation is soothing and relaxing, and a person with cancer may very well be served by investigating various meditation techniques. Alternative medicine may also be a way of harnessing the mysterious placebo effect.
Rather than relying solely on alternative medicine, however, it makes more sense to use it in combination with modern medicine. This is referred to as complementary medicine. Michael Lerner's excellent book, Choices in Healing: Integrating the Best of Conventional and Complementary Approaches to Cancer (MIT Press, 1994) gives a thorough overview of integrating conventional and complementary approaches to cancer treatments. It's available in many libraries and bookstores, as well as online, in its entirety, at: http://www.commonweal.org/choicescontents.html.
If you do choose to rely in part on complementary medicine, it's critical that you tell your doctor about it. Some "herbal" remedies, for example, contain powerful chemicals that may conflict with your other treatments. Just because something is derived from an herb or is freely available in a health-food store, it doesn't mean that it's safe.
Finally, it's a sad fact that while many alternative medicine practitioners are well-intentioned, others are despicable snake-oil salesmen who cynically exploit the credulity and desperation of people with cancer. Unfortunately, in the absence of data from valid clinical trials, it's very difficult to separate the good from the bad in alternative medicine.
If you do choose to investigate clinical trials, be sure to look carefully at the credentials of the investigators and the reputations of the sponsoring institutions.