The coming year marks the 30^th anniversary of the multi-billion dollar "war on cancer." It seems appropriate, therefore, to launch a column that critically examines claims of progress. Conventional treatment (surgery, radiotherapy and chemotherapy) has proved to be very limited in what it can accomplish. I believe that the most promising new approaches are coming from complementary and alternative medicine (CAM). I will discuss the latest CAM treatments in this column. but I also intend to scrutinize new developments in conventional therapy.

The key question is, "Does any proposed treatment really benefit cancer patients?" This may seem obvious, but proof of real benefit is lacking for most treatments. An effective treatment needs to increase overall survival while preserving or enhancing quality of life. Very often, however, the treatment simply shrinks tumors without improving overall survival. Tumor shrinkages do not usually correlate with increased overall survival in adults. This is the central fallacy of conventional oncology.

Questioning Chemotherapy Revisited

I recently completed an update of Questioning Chemotherapy. Since that book was first published in 1996, the Food and Drug Administration (FDA) has approved over 70 anticancer drugs. Most of these were slight modifications of existing medications, new indications of previously approved agents, or purely palliative drugs. In my update, I focus on a dozen new drugs that have been publicized as cancer breakthroughs. My main concern is whether these agents really benefit cancer patients by increasing their overall survival.

I focus on the results of randomized clinical trials, considered the "gold standard" of testing. I look closely at such drugs as docetaxel (Taxotere), gemcitabine (Gemzar), irinotecan (Camptostar), rituximab (Rituxan), and trastuzumab (Herceptin). Examining clinical trials, I find that the new drugs do not extend the life of the great majority of adults who receive them. But the public is systematically misled about the value of chemotherapy.

I am not alone in having doubts. Steven Hirschfield, MD, an FDA cancer expert, recently said: "Many studies done in oncology are incomplete and inconclusive" {Oncology Times, September, 2000}. This is an understatement. Clinical cancer research does not usually live up to its own professed standards of proof.

For example, I was at the American Society of Clinical Oncology meeting in May, 1998 when clinical trial results with Herceptin were unveiled. The atmosphere was electric. Herceptin became the subject of innumerable stories. An NBC correspondent wrote a book, Her-2, subtitled, A Revolutionary Treatment for Breast Cancer. He claimed that Herceptin "offers promise for hundreds of thousands of breast cancer patients." Two patients, in particular, who had had complete responses on the drug, were repeatedly paraded before TV cameras.

No surprise, then, that the FDA soon approved Herceptin as a first-line treatment for metastatic disease (combined with Taxol) or for use alone in patients who had tried chemotherapy without success. However, when we look at the actual test results with Herceptin, they are weak. In the first clinical trial, 9 out of 37 patients with advanced breast cancer "responded" after getting the new drug in combination with the drug cisplatin. According to the study authors, "the median time to progression among the responders was 8.4 months" {Semin Oncol 1999;26S:89-95}.

In another small trial, in which Herceptin was used as a single agent, there were just 5 responses out of 43 patients. The minor responses lasted 5.1 months {Semin Oncol 1999;26S:78-83}. Herceptin's poor showing in clinical trials may be why the four-page insert for the drug in medical journals says hardly a word about its effectiveness.

Herceptin was also hailed as relatively non-toxic. "Unlike chemotherapy or radiation," reads the jacket copy of Her-2, "Herceptin has virtually no disabling side effects." Yet in May, 2000, the manufacturer mailed a letter to doctors warning that the drug had been linked to 15 deaths and 47 other serious "adverse reactions" in patients, including allergic shock and extreme respiratory distress.

Society has now moved on to other wonder drugs. But detailed information about the actual outcome of clinical trials is never as widely publicized as the hype. The public is barraged with misleading stories and left with the impression that steady progress is being made. Such is the Grand Illusion of the war on cancer.

Chemotherapy Can Cause Leukemia

Chemotherapy can also have terrible long-term effects. A new study confirms that some women with breast cancer who receive chemotherapy (in addition to surgery and radiation) have a 28 times greater chance of developing leukemia than those who avoid such drugs.

French doctors looked at over 3,000 breast cancer patients treated between 1982 and 1996. Ten developed acute leukemia and all ten of these had also received chemotherapy. In comparison, women who received no chemotherapy had no increased risk {J Clin Oncol 2000;18:2836-42}. The increased risk was especially apparent in younger women who received the drug mitoxantrone (Novantrone).

"In women with early breast cancer and potential long survival, short-term beneficial effects of mitoxantrone should be weighed against possible long-term threatening side effects," the researchers concluded. Here is yet another reason that we should spare no effort to find truly non-toxic alternatives to chemotherapy.

CAPCAM Meeting

Who better to do such studies than the National Cancer Institute (NCI)? With its immense resources and experience, NCI should be in the forefront of CAM studies. But in fact NCI has had a very poor record at evaluating alternative treatments. Who can forget the tragic fiascoes of laetrile, hydrazine sulfate and Burzynski's antineoplastons? History has left a legacy as bitter as the bitterest apricot kernel.

By 1998, however, public pressure had mounted for the fair testing and reporting of alternative cancer therapies. After stormy hearings of Rep. Dan Burton's House Committee on Government Reform and Oversight, NCI Director Richard Klausner, MD, changed NCI's direction and asked members of the CAM community to advise NCI on the evaluation of new therapies.

It was a bold step. The NCI established an Office for Cancer Complementary and Alternative Medicine (OCCAM), headed by Jeffrey White, MD At the same time, the Cancer Advisory Panel on Complementary and Alternative Medicine (CAPCAM) was formed. This advisory council, made up of representatives from both conventional and complementary medicine, is under the aegis of the National Center for Complementary and Alternative Medicine (NCCAM). CAPCAM reviews and recommends non-conventional cancer treatments for further evaluation. On September 18, I took part in the third CAPCAM meeting.

The good news is that, after years of antagonism, NIH, NCI and representatives of the CAM community are finally working together to seriously investigate CAM therapies. The first fruit of this collaboration is a clinical trial at Columbia University to test the Gonzalez regimen for pancreatic cancer. After many delays, this trial is recruiting patients. NCI has been enthusiastic and NIH has contributed $1.4 million.

The bad news is that, in most other areas, progress has been agonizingly slow. The Office of Alternative Medicine (OAM) was established in 1991, and thus some of us are entering our tenth year of collaboration with the government on this issue. Yet in September, 2000, after months of effort, only one non-conventional treatment was presented to CAPCAM and its "best case series" consisted of only three cases.

There is an understandable temptation to blame everything on government inertia. But before we point fingers, we should examine the behavior of the CAM community. CAM practitioners have not yet taken NCI up on its willingness to investigate unconventional treatments. Of course, it won't be easy to heal the damage done by past blunders. But it is extremely important that we try to do so. In fact, I believe that success in the War on Cancer depends on confronting and overcoming the barriers between conventional oncology and alternative medicine.

You may think that NCI will never perform a fair evaluation of alternative treatments. As the author of The Cancer Industry, I would certainly be inclined to believe this. Yet the evaluation of Dr. Gonzalez's treatment is under way, and his protocol, which includes daily coffee enemas, could not be more controversial. Dr. Gonzalez has created a friendly relationship with Columbia University and NCI because of the rigorous way in which he presents his data.

The bottom line is: if you believe that you have a valuable alternative approach to cancer, I strongly urge you to contact Jeffrey D. White, MD at the National Cancer Institute (301-435-7980, ncioccam-r@mail.nih.gov). The resulting evaluation can only benefit the cause of complementary and alternative medicine…and of humanity, in general.

CAM Patients Make Better Patients

Last year there was a hullabaloo when some New York researchers claimed that cancer patients who used CAM were ill-adjusted and depressed. But a new study shows that CAM-using patients have better coping skills and a greater willingness to follow through even on conventional treatments. Simply put, they make better patients!

"Many oncologists fear that use of complementary and alternative medicine may lead patients to abandon medical treatment," said Dr. Wolfgang Sollner, lead author of the new Austrian report. "In our study, patients who used complementary and alternative medicine...expressed as high a trust in conventional medicine and showed as high compliance…as patients not interested in complementary and alternative medicine."

The investigators questioned 172 patients who were taking radiation therapy for cancer. Overall, 24.4 percent had already used CAM, while another 31.4 percent expressed an interest in doing so. The most popular alternatives were multivitamins, herbs and homeopathy.

In general, CAM users were younger but had a more advanced stage of their illness. They also had greater problem-solving and information-gathering skills than those who did not report such an interest. CAM offers patients a way of "avoiding passivity and of coping with feelings of hopelessness," said Dr. Sollner {Cancer 2000;89:873-80}.

This report powerfully counters clichés about CAM spread by various "quackbusters." They claim that CAM-users are weak-minded individuals who are likely to abandon conventional therapy. In fact, most CAM-users are intelligent and well adjusted individuals who choose wisely among all available treatments.

Feverfew and Chemotherapy

"An increasing body of evidence is now emerging...that some herbal medicines are efficacious," Edzard Ernst, MD, of the University of Exeter, recently said in the British Medical Journal.

In particular, herbs that decrease inflammation may increase the effectiveness and decrease the toxicity of chemotherapy. Dr. Harikrishna Nakshatri and his colleagues at the Indiana Cancer Research Institute have found some herbal compounds that can inhibit genes that are responsible for the resistance of cancer cells to chemotherapy {Oncogene 2000;19:4159-4169}.

Anti-inflammatory products that come from plants include aspirin, originally derived from white willow (Salix alba) and bridal wreath (Spiraea spp.), as well as helenalin, from a form of sneezeweed (Helenium microcephalum). But these are all somewhat toxic.

A less toxic option is to use parthenolide, an extract of the herb feverfew (Tanacetum parthenium). Dr. Nakshatri grew cancer cells in the presence of parthenolide. Cells incubated with the feverfew extract were more sensitive to the toxic drug, Taxol. This could mean reduced toxicity.

The common barberry bush, which contains the chemical berberine, is also gaining new respect as an anti-inflammatory. Few scientists know that barberry is an ingredient in the controversial Hoxsey anticancer formula. This work shows how herbal medicine may work together with conventional oncology to provide better outcomes for cancer patients.

Should cancer patients receiving chemotherapy also take feverfew or barberry? It might make sense. But please do so under the guidance of a skilled healthcare practitioner, since herbs and drugs may also interact in unexpected ways.

Despite a lot of brave talk, the cancer war is stymied. Gene therapy is only a distant hope. I believe it is time for complementary and alternative medicine to move to the fore and show what it can do. Readers who want to learn more about this approach are encouraged to sign up for my free newsletter at www.cancerdecisions.com.

Ralph W. Moss, Ph.D. is the author of eleven books on cancer topics, including Cancer Therapy and Antioxidants Against Cancer. He directs The Moss Reports, a comprehensive information service for cancer patients on treatment alternatives.