The War on Cancer: An Anatomy of Failure, by Guy Faguet, MD

Book Review by Ralph W. Moss

A prominent cancer researcher has published a trenchant critique of conventional oncology. Guy B. Faguet, MD, Professor, Department of Medicine, Section of Hematology and Oncology, Medical College of Georgia, has written The War on Cancer: An Anatomy of Failure, A Blueprint for the Future (2005).

Dr. Faguet is no stranger to cancer research. After receiving his MD degree in Bogota, Colombia, he did postgraduate work at the University of Texas and at Ohio State University. He then conducted cancer research in Augusta, GA, for 28 years, funded mainly by the National Cancer Institute (NCI) and the Department of Veterans Affairs (VA). His output has included 140 peer-reviewed articles, 7 book chapters, and two previous scientific books on cancer. He is an expert on chronic lymphocytic leukemia (CLL).

Starting about fifteen years ago, the doctor told me in a recent telephone interview, he began to develop serious misgivings concerning the lack of progress in the war on cancer. At the urging of departmental colleagues, he began writing The War on Cancer about five years ago and it was finally published by the German medical publisher, Springer, in late 2005.

Faguet has a keen sense of medical history. He points out that after the development of effective treatments for Hodgkin's lymphoma, in the 1970s, many researchers thought that the cure for the more common cancers was just around the corner. But the successful conquest of Hodgkin's disease has remained an isolated victory. "Indeed," Faguet notes, "little additional progress has been made towards the cure of most invasive cancers. In fact, in the last 20 years, only testicular cancer has been added to the short list of malignancies routinely curable using chemotherapy" (p. xiv).

How then does he explain the much-vaunted decline in the death rates for some kinds of cancer? Stomach cancer is a good example: in the early years of the 20th century, this was the most common form of internal cancer in the US, but is now relatively rare. Faguet attributes the improvement not to any dramatic advance in cancer therapy, but to "prevention and early-stage detection, to food refrigeration, to improved infection control and transfusion therapy, to enhanced nursing, social, and rehabilitation services, and to better general medical support, rather than to advances in cancer treatment" (ibid.).

In other words, general health and sanitation measures have improved survival, while there has been no change in the effectiveness of the treatment itself - a type of progress that many promoters of conventional therapies conveniently overlook.

Dr. Faguet also takes on the misleading nature of five-year survival statistics. Improvements in five-year survival are frequently cited as proof that cancer treatment is increasingly effective. One need only look at how such improvements are showcased by the American Cancer Society (Cancer Facts & Figures 2006: 17-18). For instance, for all cancers, five-year survival rose from 51 percent in 1974-76 (the beginning of the war on cancer) to 66 percent in a more recent period (1996-2001). This is the basis of claims that whereas only half of all patients survived at the start of the war on cancer, today two-thirds of patients survive their disease - an improvement that is usually ascribed to steady progress in the realm of cancer treatment, especially chemotherapy.

But, as Faguet shows, this is a gross over-simplification. "While improvements in five-year survival are frequently presented to the public and to policymakers as evidence of success in the War on Cancer, they should not be," he asserts. "This is because while survival is a valid measure of treatment outcome within a clinical trial, it is misleading when applied over long periods of time. Indeed, factors other than therapy affect survival favorably. They include improvements in supportive medical care and better screening and diagnostic tools."

An additional reason for observing improved cancer survival over the years is that, as cancer detection tools improve, cancer is diagnosed in incrementally earlier stages leading to a phenomenon called "lead time bias". Simply stated, the earlier the diagnosis the longer will patients live with their disease, giving the false impression of increased survival that can and has often been attributed to newer treatments.

Faguet also shows that cancer incidence and death rates present a very mixed picture, but in general are not falling, as we have been led to believe. In fact, if the age and size of the US (and world) population continue to increase at current rates, so too will the overall number of cancer patients. Cancer is a primarily a disease of aging populations (the average age of diagnosis for adults is 67 years), and so the graying of the baby boomers will in all probability herald a new spike in cancer incidence and mortality figures.

Faguet ascribes the general failure of the war on cancer to the application of the "cancer cell kill paradigm" that was fostered by the application of the microbial model to cancer treatment. Scientists in the late 19th century generally believed that one or more microorganisms also caused cancer. Even after this "cancer microbe" theory was broadly rejected, however, drug development and patient management continued to be based on the premise that cancer is in essence some sort of foreign invader that must be eradicated at all costs. But while it is true that in some limited cases cancer is indeed caused by a virus (such as the human papilloma virus that causes cervical cancer), in general cancer is essentially a runaway product of the human host. To paraphrase the humorist Walt Kelly, "We have met the enemy and he is us."

The cell kill paradigm holds that these "foreign" cancer cells must be eradicated like swarming germs before they overwhelm the host (p. 63). For various technical reasons, this aggressive approach has worked sufficiently well in the case of Hodgkin's disease, where a combination of four drugs (the so-called MOPP protocol) is curative in many cases, albeit at a significant cost in toxicity and second cancers. However, as Faguet points out, "this early success was seldom replicated despite a myriad of subsequent clinical trials launched to test a variety of intermittent combination chemotherapy regimens in many types of cancer over the ensuing four decades."

Chemotherapy has also cured acute lymphocytic leukemia (ALL) in children, choriocarcinoma, germ cell tumors, and a few other rare types of cancer in pediatric and young adult patients. Additionally, as an adjuvant, it modestly improves survival after surgery in a number of adult cancers. But by and large it has been a failure in treating advanced disease. As both Faguet (2005) and the Australian researchers Graeme Morgan et al. (2004) have shown, chemotherapy is responsible for curing only approximately 2 percent of those who receive it for advanced cancer.

Faguet is also critical of immunotherapy, which dominated cancer research in the 1970s and part of the 1980s. Few now remember the initial hype that greeted the emergence of interferon, interleukin, and the other so-called 'biological response modifiers' (BRMs).

"Each immune enhancer rode a wave of enthusiasm within the medical community and in the press," says the author, who himself performed scientific work on the immunological dimensions of cancer. For example, the drug interferon-alpha, a cytokine, was greeted with a deluge of media coverage, mainly thanks to its astute promoters. "It was touted as a 'magic bullet,' a 'miracle cure,' 'like the genie in a fairy tale,' that was equally good to cure the common cold or cancer," he writes. He recalls that when an article in the New York Times finally called its efficacy into question, four scientists from Sloan-Kettering Institute, New York, wrote a letter to that newspaper "expressing dismay that such reporting might undermine public support for interferon research" (p. 65).

Eventually, however, the media and the public caught on to the hype, and interferon has disappeared from the treatment of most kinds of cancer therapy (although it still has a limited role in treating a number of malignancies). This overselling of interferon should have been a cautionary tale for all concerned, yet in fact it became the model for future hype campaigns. Just a few years later came an even more extreme promotion of another cytokine drug, interleukin.

"Despite two decades of intense studies," Faguet writes, "immune stimulants have had little impact on cancer management" (p. 66). This section of the book is perhaps a bit ungenerous towards the immunological concept, which I believe still holds promise as an adjunctive treatment for cancer. In his eagerness to make his argument, Faguet gives short shrift to the great progress that has been made in the field of immunogenetics and in the development of various kinds of cancer vaccines.

Fallacies of Chemotherapy
Faguet saves his most trenchant criticism for the fallacies involved in the application of cytotoxic chemotherapy, especially high-dose treatment. His background as a researcher into these very treatments makes this part of his analysis truly compelling. He writes here with a sure hand that will certainly have the effect of increasing the ranks of those who are doubtful about chemotherapy's effectiveness.

The essential fallacy of chemotherapy, says Faguet, is "that while most patients achieve some degree of tumor response few survive longer as a result." This is certainly the essential point - the general lack of any correlation between tumor responses (especially partial responses) and overall prolongation of life. He treats the reader to a fascinating overview of the history of chemotherapy, leading up to passage of the National Cancer Act of 1971. Faguet has a clear understanding of the various forces that led to passage of that Act. But while that multi-billion legislation (NCI's budget is now $4.8 billion per year) has funded astonishing progress in the basic sciences, it has been an almost total failure in finding actual cures for common cancers.

"Three decades later," says Faguet, "the process of anti-cancer drug development remains mostly anchored on this century old, conceptually antiquated, technically inefficient, labor intensive, costly, and low-yield 'hit and miss' (mostly miss) screening approach engineered and sponsored by the National Cancer Institute (NCI)."

He shows how the National Cancer Institute's approach has been largely empirical. For example, although NCI has doggedly screened tens of thousands of potential cancer treatments, natural as well as synthetic, it has found only a handful of useful agents, almost all of which are cellular poisons. "No existing laboratory method," says Faguet, "can accurately predict the anticancer efficacy of a particular chemical..." (p. 73).

He is also strong at describing the competing and interlocking theories of cancer cell dynamics that underlie the application of toxic drugs. For many years, the dominant concepts were those of Howard Skipper, MD. These were based on test tube models that did not mimic what happened in actual human patients. Skipper's "laws" were succeeded by Mendelsohn's concept of growth fraction and the hypothesis of Goldie and Coldman on drug resistance. Oceans of ink have been spilled in disputing these conflicting theories. But, as Faguet points out, the fact is that "none of these hypotheses led to more efficacious cancer management and today the outcome of most cancer patients remains grim" (p. 78). The bottom line for any cancer theory is always its actual effect on patients' survival.

Faguet also explains how the limited progress made in treating a few cancers has been used to obscure the failure to cure more common forms of the disease. Thus, he writes, "true prolongation of survival has been achieved over the last decade or so in subsets of patients afflicted by some cancers including breast, prostate, and colon. On the other hand, favorable survival trends in many cancers observed over several decades relate to factors other than cancer treatment" (p. 89).