Oxaliplatin

An article of extraordinary importance has appeared in Fortune magazine. It is titled "Why We're Losing the War on Cancer." The author, Clifton Leaf, is Executive Editor of the magazine and is himself a survivor of adolescent Hodgkin's disease. So he is no stranger to cancer or to the potential of modern treatment to cure some of its less common manifestations.

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Leaf recognizes that he himself was extraordinarily lucky in surviving. But he still has the courage to ask, "Why have we made so little progress in the War on Cancer?" He readily acknowledges the flood of recent favorable publicity for drugs such as Gleevec, Herceptin, Iressa, Erbitux and most recently, Avastin. "[T]he cure has seemed closer than ever," he acknowledges.

"But it's not," he continues. "Hope and optimism, so essential to this fight, have masked some very real systemic problems that have made this complex, elusive, relentless foe even harder to defeat.... [W]e are far from winning the war. So far away, in fact, that it looks like losing."

Leaf gives some facts about cancer that are well known to insiders but will come as a shock to many readers:

* More Americans will die of cancer in the next 14 months than have died from every war that the US has fought ... combined.

* Cancer is about to replace heart disease as the number one US killer. It is already the biggest killer in many age groups.

* Even adjusting for age, the percentage of Americans dying from cancer is about the same as it was in 1971 (when Nixon declared the war on cancer) or even back in 1950! Meanwhile, age-adjusted deaths from heart disease have been slashed by 59% and from stroke by 69% during that same half-century.

The much vaunted improvement in survival from cancer is largely a myth. "Survival gains for the more common forms of cancer are measured in additional months of life," says Leaf, "not years."

* Most of the improvement in longevity of cancer patients can be attributed to lifestyle changes (the promotion of which has not been a conspicuous priority for the National Cancer Institute) and especially to early detection.

* The few dramatic breakthroughs (such as in Hodgkin's disease) mainly occurred in the early days of the war on cancer. There has been little substantial progress in recent decades ... despite nearly ubiquitous claims to the contrary.

* According to one biostatistician at M.D. Anderson Cancer Center, long-term survival from common cancers such as prostate, breast, colorectal and lung "has barely budged since the 1970s."

* According to Andy Grove, the chairman of the Intel corporation and a major "player" in funding research, "It's like a Greek tragedy. Everybody plays his individual part to perfection, everybody does what's right by his own life, and the total just doesn't work."

Today, Leaf concludes, the cancer effort is "utterly fragmented--so much so that it's nearly impossible to track down where the money to pay for all this research is coming from." And what money! Leaf estimates that US $14.4 billion is spent each year on cancer research. "When you add it all up, Americans have spent ... close to $200 billion, in inflation-adjusted dollars, since 1971." It is certainly justifiable to ask for an accounting of that one-fifth of a trillion dollars.

Irrelevant Research

What have we gotten for that huge sum? In fact, research has become increasingly irrelevant to the real-life problems faced by cancer patients. "The narrower the research niche," says Leaf, "the greater the rewards the researcher is likely to attain." Particularly disturbing is his assertion that cancer research is fundamentally flawed in its orientation. Cancer scientists have self-confidently created "animal models" and artificial cell lines that supposedly mimic an equivalent human disease, such as breast, colon or lung cancer. These scientists then triumphantly "cure" cancer in these laboratory models. But cell lines and tumors growing in mice are drastically different from spontaneous human tumors, the kind that afflict us and our loved ones. A flawed model is not likely to yield useful results. Those who closely follow the cancer field have become inured to an endless series of "breakthroughs" in mice that almost never pan out when tried in the clinic.

According to one of America's most celebrated cancer researchers, Dr. Robert Weinberg of the Massachusetts Institute of Technology (MIT), "a fundamental problem which remains to be solved in the whole cancer research effort, in terms of therapies, is that the preclinical models of human cancer, in large part, stink."

Prof. Bruce Chabner of Harvard University expressed similar frustration: "Cancer researchers say, 'I've got a model for lung cancer!' Well," says Chabner, "it ain't a model for lung cancer, because lung cancer in humans has a hundred mutations. It looks like the most complicated thing you've ever seen genetically."

Why then are these artificial and intrinsically misleading systems still being used? The answer is simple. These artificial models are "... very convenient, easily manipulated," says Vishva Dixit of the Genentech company. "You can assess tumor size just by looking at [them, ed.]." There's no thought, still less acknowledgement, given to the fact that shrinking a tumor, especially in a mouse, has little to say about human survival or well-being.

"Hundreds of millions of dollars are being wasted every year by drug companies using these models," says Weinberg. But with the huge profits to be made from tumor-shrinking drugs like Avastin, Erbitux and oxaliplatin, what incentive do they have to stop?

Shrinking Tumors

Leaf also tackles the subject of cancer regression, or shrinkage of tumors, pointing out that it is a totally inadequate measure of the effectiveness of a drug. "It is exciting to see a tumor shrink in mouse or man and know that a drug is doing that," says Leaf. "It is a measurable goal." But, he adds, "tumor regression by itself is actually a lousy predictor for the progression of disease." The sad truth is that "regression is not likely to improve a person's chances of survival." Read those words over carefully--you do not get to read such ideas often in mainstream publications.

By contrast, what really matters, says Leaf, is stopping metastases (secondary growths), which kill the great majority of cancer patients. "So you'd think that cancer researchers would have been bearing down on this insidious phenomenon for years," he says. In reality quite the opposite is true. Fortune magazine's examination of NCI grants, going back to 1972, revealed that less than 0.5% of study proposals focused primarily on metastases. Half of one percent! Of nearly 8,900 grant proposals awarded last year, 92% didn't even mention the word metastasis.

According to I.J. (Josh) Fidler of M.D. Anderson, the study of metastases is avoided by cancer researchers because it is a tough and so far unfruitful field, and not likely to yield quick and easy results. Instead, researchers focus on techniques and avenues that they know will produce measurable results in the laboratory. The attitude, Fidler says, is "Here's an antibody I will use, and here's blah-blah-blah-blah, and then I get the money." The current crop of new drugs comes in for scathing criticism as well. A study done in Europe showed that 12 new anticancer drugs approved in Europe between 1995 and 2000 were no better in terms of improving survival, quality of life, or safety, than those they replaced. But as far as the drug companies were concerned they had one big advantage: they were several times more expensive to purchase than the old drugs. "In one case," says Leaf, "the price was 350 times higher."

Leaf points out that two new blockbuster drugs, Avastin and Erbitux, are lacking in substantial effectiveness. Avastin, he says, "managed to extend the lives of some 400 patients with terminal colorectal cancer by 4.7 months." And Erbitux? "Although it did indeed shrink tumors, it has not been shown to prolong patients' lives at all." Still, a weekly dose costs $2,400.

The article then features a list of "Miracle Cures That Weren't," including radiation therapy, interferon, interleukin-2, endostatin and Gleevec. As Leaf himself admits, Fortune itself once featured Interleukin-2 on its cover with a huge headline reading: "Cancer Breakthrough."

Yet despite the profound importance of what Leaf has to say in this article, you are unlikely to see the article cited as front-page news. I was dismayed to find that the total number of citations at Google News for this article was three (out of 4,500 news sources). By comparison, at the time of its announcement Erbitux was generating over 1,000 articles per day in the same search engine.

However, excellent though this article is, and delighted though I am to see this subject aired so prominently, I do regret the fact that Leaf did not take his arguments quite far enough. For instance, Leaf includes a section on "how to win the war," but this seems anemic and hard to follow compared to his previous incisive analysis. In my opinion, he doesn't deal with the basic economic and political underpinnings of the war on cancer. The emphasis on ever-more-profitable drugs is dictated by the very nature of Big Pharma and its unhealthy influence on the whole research and approval apparatus.

Also, Leaf fails to cite the most prominent critics of the war on cancer, especially those with an orientation towards complementary and alternative medicine (CAM). Thus, while he hits the nail squarely on the head in many instances (as, for example, when he discusses the danger of equating temporary tumor shrinkages with increased survival), he also misses many other important aspects of the problem that are well-known to people who have followed this field for decades.

When he quotes a scientist as saying, "We have a shortage of good ideas," this is likely to elicit incredulity from the CAM community. There are scores of excellent researchers who have proposed exciting new ideas for treating cancer over the last few decades. Most of them have been ignored or dismissed out of hand. Many treatments discussed in my books The Cancer Industry (1980), Cancer Therapy (1992) and Antioxidants Against Cancer (2000) have still not been examined, much less acted upon.

Let me give one example of an original idea that has been studiously ignored by the mainstream. I recently received a reprint from my colleagues Eva and Laszlo Csatary, MD, of their latest results using MTH-68. This treatment is based on the non-toxic Newcastle disease virus vaccine and is seemingly quite beneficial in select cases, especially of brain cancer. The article appears in a recent issue of the Journal of Neuro-Oncology, with co-authors from respected institutions in Germany, Hungary and California. It is not the first such article that Dr. Csatary has published. I myself co-authored a best case series with him on this topic in 1999, which appeared in a respected peer-reviewed journal. Admittedly, this is not exactly a "new" idea, simply an unrecognized one. In fact, the name of the compound, MTH-68, refers to the date of first discovery ... 1968, three years before the war on cancer was launched, and before many of today's cancer researchers were even born. Despite repeated articles and letters, press releases, news conferences and appeals to governmental authorities, this promising treatment has made little progress in the world of conventional medicine. The response from the American "cancer establishment" to the Csatarys' work has been a thundering silence.

This June, 25,000 oncologists are gathering at the American Society of Clinical Oncology (ASCO) meeting for their annual four-day convention. Don't expect any center-stage attention, though, for promising non-toxic treatments, such as MTH-68, which could provide true departures from the quagmire of the stalled war on cancer. Even Mr. Leaf, for all his trenchant criticism, seems unaware or unconcerned that there are many other treatments that are potentially valuable, yet are being systematically ignored. And they will continue to be ignored until the public, Congress and scientific community wake up to the fact that the most powerful force driving cancer research is Big Pharma's need for a hefty bottom line and a quick return on their investments.

It is enough to make the angels weep.

Bibliography

Csatary LK, Moss RW, Beuth J, et al. Beneficial treatment of patients with advanced cancer using a Newcastle disease virus vaccine (MTH-68/H). Anticancer Res. 1999 Jan-Feb;19(1B):635-8.

Csatary LK, Gosztonyi G, Szeberenyi J, et al. MTH-68/H Oncolytic Viral Treatment in Human High-Grade Gliomas. Journal of Neuro-Oncology 2004;67:83-93.

Leaf, Clifford. Why we're losing the war on cancer. Fortune 2004;149(6):76-97.

by Ralph W. Moss, PhD, Director, The Moss Reports

[c]2004 Ralph W. Moss, PhD. All Rights Reserved

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