There was a time when The New York Times could be counted on to invariably promote the US government's "war on cancer." In previous decades, it touted every hopeful sign of progress and often conveyed the feeling that a cure was around the next corner.
Many readers will recall the celebrated May 1998 article in which the Times announced two new drugs with this headline: "Hope in the Lab: A Cautious Awe Greets Drugs That Eradicate Tumors in Mice." The article concerned two new agents, endostatin and angiostatin, developed by Harvard Professor Judah Folkman, MD. The author, veteran science writer Gina Kolata, quoted the director of the National Cancer Institute (NCI) as saying that Folkman's work was "the single most exciting thing on the horizon for the treatment of cancer."
James Pluda, MD, also of the NCI, said, "People were almost overwhelmed" by Folkman's presentation. "The data were remarkable." The Nobel laureate James D. Watson, MD, famously told Kolata, "Judah is going to cure cancer in two years." But the millennium came and went without a cure. Angiostatin and endostatin have not lived up to expectations. For instance, a clinical trial in 40 patients at Dana-Farber Cancer Institute, Boston, came up empty-handed. The investigators concluded that treatment with endostatin "did not result in significant tumor regression in patients with advanced neuroendocrine tumors" (Kulke 2006).
Not Going Well
Now Ms. Kolata has made waves again, albeit in a much more sober tone. Her front-page article on April 24, 2009, marked a turning point, as she described for Times readers a litany of failures in the war on cancer over the past few decades. The overall death rate for cancer, she revealed, when adjusted for the size and age of the population, dropped only 5% from 1950 to 2005. "In contrast," she wrote, "the death rate for heart disease dropped 64 percent in that time, and for flu and pneumonia, it fell 58 percent."
"Still," she wrote, "the perception, fed by the medical profession and its marketers, and by popular sentiment, is that cancer can almost always be prevented. If that fails, it can usually be treated, even beaten." I too wrote about this gap between perception and reality in my first book, The Cancer Industry, which came out in 1980. At that time, I was frustrated by the uninformed attitudes towards the war on cancer that I found at America's "newspaper of record." I am certainly encouraged that, 30 years later, the Times is finally waking up to the fact that things are not going well in the war on cancer.
Kolata focuses on the treatment of metastatic cancers. "With breast cancer, for example, only 20 percent with metastatic disease – cancer that has spread outside the breast, like to bones, brain, lungs or liver – live five years or more, barely changed since the war on cancer began."
The situations with colon, lung, and prostate cancer are no better, said Kolata: "With colorectal cancer, only 10 percent with metastatic disease survive five years. That number, too, has hardly changed over the past four decades. The number has long been about 30 percent for metastatic prostate cancer, and in the single digits for lung cancer" (2009). These are the grim facts, despite $105 billion spent by the NCI on the war on cancer since its inception in December 1971.
Where Does the President Stand?
As is well known, President Barack Obama lost his mother, Ann Soetoro, and his grandmother, Madelyn Dunham, to cancer. He is as well informed about the ravages of this disease as any president in modern times. He has spoken repeatedly about his desire to see cancer cured soon. He has also vowed that, as part of the economic stimulus package, he will increase federal funding for cancer research by a third for the next two years.
I also believe in generously funding cancer research. However, if the decades-long "war on cancer" has taught us anything, it is that providing billions of dollars for research is not in itself a sufficient stimulus to real progress. What is far more important is the quality of the treatments being pursued. So far, the NCI has focused its formidable resources on helping develop synthetic and patented pharmaceutical agents that can then be sold at astronomical prices. I am thinking here of the so-called targeted drugs, such as bevacizumab (Avastin), which costs about $100,000 per year per patient.
Obama should examine the manner in which promising drugs are selected for development. As a rule, the NCI works hand-in-glove with giant pharmaceutical companies (or their surrogates) to research and develop new products. This cozy relationship with big business has left behind some of the most promising treatments that do not fit the mold. These are primarily treatments of natural origin that are not patentable or otherwise profitable to Wall Street. It is a case of "patents over patients" (as I wrote in my New York Times op-ed piece two years ago). This overemphasis on satisfying the needs of the stock market has fostered a greedy mentality in the cancer field as well. Sometimes, the purpose of performing research has become to generate profits, not to cure cancer in the most expeditious manner possible.
Unless the Obama administration grasps that there is a fundamental problem beyond the lack of research funding, it is unlikely to accomplish anything significant in the cancer field. The administration is still in its early days. But I wonder if the president is hearing this message from his medical advisors, such Ezekiel Emanuel, MD, brother of his chief of staff, who is a breast cancer oncologist and medical ethicist at the NCI.
If I had some time alone with President Obama, I would tell him that there are promising treatments for cancer that are awaiting development but have been neglected because they are deemed insufficiently profitable to big companies. The president has stirred the entire world with his promises of change. When it comes to cancer, however, the White House needs to support and promote treatments based solely on their merits, without regard to the profits of Wall Street or the medical profession. That indeed will be change I can believe in.
Institute Questions Adriamycin
The NCI has issued a very negative report on the drug Adriamycin (doxorubin) as well the other anthracycline drugs (epirubicin and idarubicin). As I reported in my online newsletter in 2007, prominent oncologists had begun to warn their colleagues and the public that use of this toxic class of drugs was unnecessary in as many as 92% of the breast cancer patients who received it. This point of view has now been given powerful support by a new Canadian study in the Journal of the National Cancer Institute (JNCI; O'Malley 2009), with an accompanying editorial by Dennis J. Slamon and Michael F. Press (2009).
The authors of the new article studied 438 tumor specimens from premenopausal women who had node-positive breast cancer and were given adjuvant chemotherapy after surgery. All the women received either a regimen known as "CEF," which contained, in addition to the standard drugs cyclophosphamide and 5-FU, epirubicin (an anthracycline); or an older regimen, "CMF," which contained, in addition to cyclophosphamide and 5-FU, the non-anthracycline methotrexate.
Scientists then looked for the presence or absence of certain markers on the cancer cells, called TOP2A and HER2. Their key finding was that patients whose tumors showed changes in these markers did indeed survive longer after receiving CEF (the anthracycline-containing regimen) than those treated with CMF. But they also showed that patients who did not have TOP2A changes had no significant improvement in survival (O'Malley 2009).
As Slamon and Press (2009) commented in their accompanying editorial:
This report is the latest in a series of publications that question the generalized assumption that there is an incremental benefit to all breast cancer patients who receive anthracycline-based adjuvant therapy as opposed to non-anthracycline-containing adjuvant therapy.
This remarkable editorial is available free of charge at the JNCI Web site. I urge all readers who are seriously interested in this question to study it carefully. It contains much fascinating information on how the anthracyclines became part of the standard of care for adjuvant breast cancer chemotherapy.
Why does all this matter? Even in the world of toxic chemotherapy, Adriamycin and its fellow anthracyclines are notoriously dangerous: Slamon and Press refer to the "well-known, long-term, and life-threatening problems associated with anthracyclines." These adverse effects include cardiac toxicity, such as congestive heart failure, as well as bone marrow dysfunction, including acute leukemia and myelodysplasia. These serious adverse effects have long been known. However, Slamon and Press present data showing that "longer follow-up ... of breast cancer patients who received adjuvant anthracyclines for their breast cancers indicates that our initial assessments may have underestimated these long-term toxicities" (2009). In other words, the news about the long-term effects of anthracyclines is worse than we thought.
Slamon and Press make the further point that earlier assessments of the risks and benefits of adjuvant chemotherapy lumped all patients together in a rather crude way. "We now know that the molecular diversity of human breast cancers is much more complex and that clinical benefits derived from various systemic therapeutic interventions can be profoundly affected by the molecular subtype of the disease."
Since 2007, Slamon in particular has been courageously warning about the danger of the anthracyclines and calling for individualizing cancer treatment based on molecular characteristics of the tumor. I wholeheartedly agree. But I would argue that the issue is even larger. Oncology (like modern medicine in general) tends to put patients into cookie-cutter molds. The reason may be economics – it is more cost-effective to treat patients en masse with minimal time spent dealing with their individual characteristics.
But modern science (not to mention ancient humanism) tells us that each person is different, and that treatment should be individualized based on all aspects of the person. The molecular characteristics of the tumor are one important new part of that. But I would argue that this individualization should include chemosensitivity testing of tumors, the creation of autologous vaccines, and a more holistic approach that takes into account the psychological and social needs of the patient.
Coley's Toxins: The Sum of Our Hope
Coley's toxins were – and are – among the most promising cancer treatments ever devised. They have existed in one form or another for over 100 years. But since the 1960s they have been effectively banned in the US, although they are still available in several other countries (including Mexico and Germany).
What exactly are Coley's toxins (also called mixed bacterial vaccine)? They are a powerful stimulator of the immune system made up of the killed byproducts (or "toxins") of two potent bacteria. The first of these is Streptococcus pyogenes, which causes the skin disease erysipelas, among other illnesses. The other is Serratia marcescens, which potentiates the action of other bacteria and has independent anticancer activity.
After observing that the skin disease erysipelas sometimes triggers the "spontaneous" regression of tumors, William B. Coley, MD (chief of the bone cancer service at what is now Memorial Sloan-Kettering Cancer Center in New York), began to use a killed mixture of bacteria in the treatment of cancer. For many years, Coley's toxins were manufactured by the Parke-Davis Co. and grudgingly accepted by the American Medical Association (AMA). After Coley's death in 1936, his son, Bradley, inherited his practice and continued to use the toxins until the early 1960s. But after passage of strict new amendments to the Food and Drug Act, the FDA refused to "grandfather" Coley's treatment (i.e., accept them as a long-established part of medicine, as they did, for instance, with aspirin) but banned them as a "new drug." This "new drug" was at that time almost 75 years old.
At my website, www.cancerdecisions.com, the reader will find a new 100-page report on Coley's toxins, with its many illustrations and 285 footnotes. The Coley story is a human drama of the greatest importance in understanding the struggle between the conventional and alternative trends in cancer research. It is also a collective tragedy, since a branch of the US government, the FDA, effectively destroyed this promising treatment and it is not widely known, researched, or used today.
In writing this report, I interviewed some of the world's experts on Coley's toxins and elicited their thoughts on the safety and effectiveness of this treatment. It is a great pleasure for me to publish a full account of Coley's toxins, which will undoubtedly come as a revelation to readers who suspect that there are more promising treatments available than the limited options usually offered by standard oncology.
Conklin K. Coenzyme Q10 for prevention of anthracycline-induced cardiotoxicity. Integr Cancer Ther. 2005;4:110–130.
Kolata G. Forty Years' War: Advances prove elusive in the drive to cure cancer. New York Times, April 23, 2009. Available at: http://tinyurl.com/pk9maa.
Kolata, G. Hope in the lab: a special report: a cautious awe greets drugs that eradicate tumors in mice. New York Times, May 3, 1998. Available at: http://tinyurl.com/qeyadw. (Bad link: http://www.nytimes.com/1998/05/03/us/hope-lab-special-report-cautious-awe-greets-drugs-that-eradicate-tumors-mice.html?scp=1&sq=&st=nyt )
Kulke MH, Bergsland EK, Ryan DP, et al. Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors. J Clin Oncol. 2006;24:3555–3561.
Marchione M. Fewer breast patients may need chemo. Associated Press. December 13, 2007. Available at: http://tinyurl.com/marchione1.
O'Malley FP, Chia S, Tu D, et al. Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. J Natl Cancer Inst. Epub 2009 Apr 28. Available at: http://tinyurl.com/cuyxrp. (Bad link: Full text requires membership: http://jnci.oxfordjournals.org/cgi/reprint/101/9/644 )
Slamon DJ, Press MF. Alterations in the TOP2A and HER2 genes: association with adjuvant anthracycline sensitivity in human breast cancers. J Natl Cancer Inst. 2009 May 6;101(9):615–618. Epub 2009 Apr 28. Available at: http://tinyurl.com/rb9n2o.