BEN'S forward to: "Beyond the Magic Bullet

Although the past twenty years have seen considerable progress in the treatment of some cancers, others have remained intractable. Among the worst are pancreatic cancer, metastatic melanoma, and glioblastoma multiforme, a type of brain cancer that I myself was diagnosed with over sixteen years ago. These are still considered death sentences, as are many other cancers once they have spread.

Why some forms of cancer are more treatable than others is not well understood. Cancers vary in the number of their genetic mutations, with the presumption that those with many mutations will make the task of finding effective treatments more difficult. Even when some aberrant growth pathways can be inhibited or eliminated, others remain and become amplified by the process of evolutionary selection. As a result, most oncologists agree thtat single-agent treatments are unlikely to be successful. This opinion is buttressed by the recognition that some forms of cancer treatment have been revolutionized by the development of treatment cocktails. For cancers such as childhood leukemia, cocktail therapy has been far more effective than treatments based on individual agents. 

Unfortunately, current policy regulating the development of new treatments has largely been based on a single-treatment mentality. Initial clinical trials almost never involve combinations of treatments, which occur only when the individual single agents have shown some degree of effectiveness. This policy thwarts effective cancer treatment in several ways. The most obvious is that it greatly slows the development of the treatment cocktails that will be necessary for cancer treatment to be successful. It also creates false negatives, as drugs that can be effective components of a treatment cocktail may not be effective as single agents. It may also make the eventual use of a treatment cocktail less effective, as the development of resistance to treatment agents presented individually causes the cocktails that contain these agents as components to be less effective.

Yet, patients, with the help of their oncologists, need not settle for the snail's pace of the development of new treatments. We now know that many medications developed for various medical conditions other than cancer possess anti-cancer properties. Because they are off-patent, many of these drugs are never tested in conventional cancer clinical trials so that the revenue generated by their anti-cancer usage does not justify the enormous cost of conducting the trials. Moreover, many foods and dietary supplements also have significant anti-cancer properties. Thus, as Dr. Chang proposes in this book, "we may not need newer and better drugs for cancer, but rather a better way of using what we already have. Based on my own experience and that of patients whom I have advised, I believe that existing knowledge about the anti-cancer properties of non-standard treatment agents may be enough for the development of effective treatment cocktails now, not some distant time in the future."

The great majority of patients who have sought to use treatment cocktails have received minimal cooperation from their oncologists. One reason for this is that medical dogma requires treatments to pass the test of randomized clinical trials before they can be used as treatments outside of clinical trials. In actuality, there is no absolute legal basis for this restriction, any physician can legally prescribe an FDA-approved drug for any purpose, not just for the purpose for which the drug was initially approved. However, doctors tend to be conservative and in fear of unnecessary liability when they do not follow standards of practice. Furthermore, insurance companies often do not pay for off-label treatments.

"When diseases have been persistently intractable to the best standard of care, as defined by conventional medical standards, common sense dictates that we enlist all possible treatment resources, not just those that have passed the test of trials."  Other forms of evidence can also be convincing, and randomized clinical trials themselves have their own problems of interpretation. Phase II clinical trials, which are not usually randomized, contain a rich source of information, as do experimental results from animal models, especially with respect to possible synergies between treatment agents.

Given that oncologists, in general, have tacitly accepted the principle that treatment cocktails may be necessary for effective treatment of many types of cancer, what explains the opposition to their use There is, of course, no opposition after an effective cocktail has been identified in well-controlled clinical trials. However, their preliminary development will have highly variable components, depending on the interpretation of the existing evidence regarding synergy among the individual components. Therefore, doctors who use cocktail treatments in their clinical practice do so under the cloud of being unscientific and at risk of being labeled proponents of alternative medicine, which carries a significant stigma among the conventional medicine concedes that it offers no effective treatments. 

When I was diagnosed with glioblastoma multiforme sixteen years ago, conventional treatment offered no hope that I could survive my disease. But "it seemed obvious to me that the HIV cocktail offered a model for how to proceed. My approach was thus to identify those treatment agents that had been shown to have some degree of efficacy for my disease and combine as many as possible." Yet I could follow this path only by surmounting the obstacles imposed by my physicians. What I needed then, and what continues to be needed by patients today, is a physician like Dr. Chang, who has a broad knowledge of different treatment modalities and appreciates the importance of treatment combinations.

Dr. Chang, as he humbly emphasizes, did not invent the idea of cocktail therapy for cancer treatment, but he has taken an important first step towards scientifically justifying its use. In Beyond the Magic Bullet, he eloquently explains why the cocktail approach is superior to the linear, or "one-drug-at-a-time," strategy that dominates present cancer care. Dr. Chang's book will hopefully advance the discussion of the cocktail strategy so that it can one day become a standard practice in cancer therapy and ease the burden of patients seeking effective treatment.