Are 'Alternatives' Good Medicine?

Plug the terms "alternative" and "cancer" into Google and the Internet search engine returns a list of 3.4 million -- yes, million -- sites with information both credible and questionable about nontraditional treatments for cancer. What's a cancer patient to make of such a vast array of options?

This "vast array" is known collectively as complementary and alternative medicine, or CAM. And the issue of how patients find information about CAM therapies is important, experts say, because not all are created equal. While some can be genuinely helpful to patients in treatment or remission, others are outright dangerous. Still others are too poorly studied to tell. Nevertheless, huge numbers of cancer patients use these therapies.

"I would guess that over 80% of cancer patients use some form of complementary or alternative therapies," says Barrie Cassileth, PhD, chief of the Integrative Medicine Center at Memorial Sloan-Kettering Cancer Center in New York. "Patients can't distinguish which are good and which are harmful, and we've got to help them do that."

To that end, experts from around the country have collaborated to form the Society for Integrative Oncology. This new professional group is a joint effort of 3 major cancer centers with strong CAM programs -- Memorial Sloan-Kettering, MD Anderson Cancer Center in Houston, and Boston's Dana-Faber Cancer Institute -- as well as other cancer-related organizations, including the American Cancer Society. The new group holds its first conference in November.

The goal, says Cassileth, president of the Society for Integrative Oncology, is to promote high-level research of CAM and to get reliable information to doctors so they can guide their patients.

The Good, the Bad, the Unknown

Some complementary therapies that patients use in conjunction with traditional cancer treatments -- like chemotherapy, surgery, and radiation -- can be very helpful, Cassileth said.

Acupuncture, for example, has been shown to be effective at reducing nerve pain, and is being tested as a remedy for hot flashes for women who can't take hormones (such as breast cancer patients). Mind-body therapies like meditation and hypnosis are being studied as ways to help control pain from medical procedures. Music therapy can help relieve depression in patients who are having stem cell transplants.

Doctors also need to know which therapies are bogus and potentially dangerous -- treatments typically considered "alternative" because patients may use them instead of scientifically studied treatments.

An article earlier this year in CA: A Cancer Journal for Clinicians (Vol. 54, No. 2: 110-118) reviewed the evidence for nearly a dozen alternative cancer therapies and found that they don't hold up under scrutiny. Among the therapies investigated were high-dose vitamin C, laetrile (a compound made from apricot pits), shark cartilage supplements, and the Gerson regimen (a purportedly detoxifying combination of diet and coffee enemas).

Such therapies should no longer be considered "unproven," wrote author Andrew Vickers, PhD, of Memorial Sloan-Kettering. Rather, "it is time to assert that many alternative therapies have been 'disproven,' " he said.

Then there are treatments that fall somewhere in between the "proven" and the "disproven" -- many herbs, for instance.

"Botanicals have tremendous potential, but they need to be studied," Cassileth said. "At this point, patients only have access to what's available over the counter in the form of supplements, but those are not a good idea to try and should be avoided because of their potential to interact negatively with traditional therapy."

Research is being conducted, she said, but the process is slow.

Not Necessarily Risk-Free

Despite the unknowns, herbal supplements are extremely popular. As many as 6 in 10 cancer patients use these remedies, according to some studies.

And quite often they don't tell their doctors about it. In one study, for instance, out of MD Anderson, researchers found that nearly half of women being treated for breast and gynecologic cancers used some type of herbal or vitamin supplement (Journal of Clinical Oncology Vol. 22, No. 4: 671-677). Yet only about half of these women informed their doctor.

"We kind of knew that patients weren't telling physicians about CAM use," said co-researcher Judith Smith, PharmD, BCOP. "Most of them don't even consider it medication."

Indeed, less than a third of the women in the study thought of herbal products and vitamins as medication. Botanicals may be "natural," but they aren't necessarily risk-free.

A review by National Cancer Institute researchers published in the Journal of Clinical Oncology (Vol. 22, No. 12: 2489-2503) suggests that many of the most common herbal products have the potential to interact with cancer drugs -- either by diluting their effect so a patient is undertreated, or by amplifying it, resulting in the possibility of overdose.

The review focused on the top-selling herbal preparations in the US: garlic, ginkgo, echinacea, soy, saw palmetto, ginseng, St. John's wort, black cohosh, cranberry, valerian, milk thistle, evening primrose, kava, bilberry, and grape seed.

Much of this research has been performed in lab samples or in animals, lead author Alex Sparreboom, PhD, emphasized; evidence from human trials is scarce, so doctors don't know for certain that any of these products will react dangerously with cancer drugs.

Nevertheless, patients and doctors should use caution, experts say, and keep the lines of communication open.

Doctors Don't Ask, Patients Don't Tell

Doctors should question cancer patients about CAM use and monitor them for unusual symptoms or reactions, said William Figg, PharmD, co-author of the herbal review.

"I think the best thing to do is to be aware that patients are likely taking [herbal supplements] and be aware they might not tell you about it," he said..

Sparreboom suggested doctors keep a list of potentially troublesome compounds, such as those noted in his review, to ask patients about.

Smith agreed that doctors need to take an active role in talking to patients about CAM. In her study, most of the women who didn't talk to their doctor about CAM use said it was because the doctor never asked about it.

But patients also must be forthcoming, Smith said, not just about CAM, but about all over-the-counter medications.

"I don't think the onus should totally be put on physicians, although they should be asking," she said. "Patients should be telling doctors everything they're taking and consulting with a physician before trying something new, particularly if they have other [conditions] like diabetes or high blood pressure."

Estrogen-Plus-Testosterone Therapy Increases Breast Cancer Risk

Women who take the hormones estrogen and testosterone in tandem to treat symptoms of menopause appear to have an increased risk of breast cancer, researchers report.

The finding are published in the July 24 issue of the Archives of Internal Medicine.

Another report in the same journal issue finds that alternative therapies to hormone replacement therapy (HRT) don't seem to work.

In the first report, Rulla M. Tamimi, of Brigham and Women's Hospital in Boston and Harvard Medical School, and her colleagues collected data on 121,700 women, who were part of the Nurses' Health Study. The researchers looked at the long-term effects of estrogen-plus-testosterone therapy.

"Estrogen plus testosterone increases the risk of breast cancer," Tamimi said. "There needs to be other studies to support these findings, but there does seem to be an increased risk, and women and their physicians should weigh the risks and benefits of estrogen-plus-testosterone therapy before starting," she said.

There is some evidence that many of the symptoms of menopause --including decreased sex drive, mood swings and poorer quality of life, such as hot flashes, night sweats, vaginal dryness and sleep problems -- are related to this decline in testosterone, the authors noted. Previous clinical trials had shown that testosterone in combination with estrogen may reduce these symptoms and promote bone health.

The increased breast cancer risk associated with testosterone may be because enzymes in breast tissue convert testosterone to estradiol, an estrogen-like hormone that could contribute to the development of breast cancer, the authors said. Higher levels of testosterone alone have also been linked to increased breast-cancer risk in postmenopausal women.

Currently in the United States, there is only one estrogen-plus-testosterone therapy available, but such treatments are expected to increase in coming years, according to the report.

During 24 years of follow-up for the study, there were 4,610 cases of breast cancer. The 29 women who were taking estrogen plus testosterone had a 77 percent higher risk of developing breast cancer than those who never used hormone therapy, the researchers reported.

The risk associated with this combination therapy was higher than the risk associated with estrogen therapy (15 percent) and of estrogen-plus-progestin therapy (58 percent), Tamimi said.

Looking only at women who had gone through menopause naturally rather than those who had had a hysterectomy, Tamimi's group found that the 17 women who took estrogen plus testosterone had 2.5 times the risk of breast cancer compared with those who had never used hormones.

One expert doesn't think that, in most cases, testosterone should be prescribed for women.

"We have always been careful about prescribing testosterone to women, based on unknown risks," said Dr. Hugh Taylor, an associate professor of obstetrics and gynecology at Yale University School of Medicine. Testosterone doesn't appear to offer a benefit much beyond a placebo effect, he added.

"We have always been hesitant about using it, and this re-enforces it," Taylor said. "The usual reason women request testosterone is for decreased libido. But for most women, decreased libido is not due to decreased testosterone. It's due to a myriad of other problems."

Concerns about hormone-replacement therapy were first raised in 2002 by the Women's Health Initiative, the landmark study involving 27,000 participants that caused many women to discontinue their use of hormone therapy.

In the second study in the journal, researchers who reviewed 70 previous studies of alternative and complementary therapies for menopause-related symptoms found there was insufficient evidence that these therapies relieve menopause-related symptoms.

"There is a significant placebo effect in almost anything that is used for the management of menopause," said study lead researcher Dr. Anne Nedrow, of the Oregon Evidence-based Practice Center and Oregon Health and Science University. "There is a lack of any evidence that of the millions and millions of dollars spent on alternative therapies that anything really works.

Nedrow's group looked at 48 studies that examined vitamins, proteins, complete diets or other biologically based treatments; nine studies that focused on mind-body therapies, including meditation and guided imagery; one study of osteopathic manipulation, a body-based therapy; two that looked at the energy-based treatments reflexology and magnet therapy; and 10 that assessed whole medical systems, such as traditional Chinese medicine or ayurvedic medicine, a traditional therapy from India.

Nedrow said the study found there really aren't any good alternative or complementary choices for women going through menopause. "The truly symptomatic women may need to reconsider estrogen," she said. "Or we may want to take advantage of the placebo effect, which has shown a 50 percent reduction in symptoms in 12 weeks," she added.

Nedrow said she doesn't think there's any harm in using alternative therapies. She recommended black cohosh or soy supplements, with the understanding that most of the effect would be a placebo effect.

One expert agreed that the benefit of alternative therapy to relieve menopausal symptoms is largely a placebo effect.

"Currently, the best medication we have to remove menopausal symptoms is estrogen," said Dr. Jennifer Wu, an obstetrician/gynecologist at Lenox Hill Hospital, in New York City. But, she added, "The associated risks make it less than desirable."

Traditional Heart Risk Factors Outdo Biomarkers

The sophisticated biomarkers for cardiac risk that have enthralled researchers in recent years don't add much diagnostic power to such traditional risk factors as blood cholesterol levels, smoking, blood pressure and obesity, a new study finds.

"Our results indicate that, at least for clinical use, they are not ready for prime time," said study author Dr. Thomas J. Wang, an assistant professor of medicine at Harvard University and a member of Massachusetts General Hospital's cardiovascular division. The report is published in the Dec. 21 issue of the New England Journal of Medicine.

Wang and his colleagues followed 3,209 participants in the Framingham Heart Study for a decade, measuring biomarkers that included C-reactive protein, homocysteine, urinary albumin, fibrinogen and natriuretic peptides.

While those measurements did provide indicators of increased risk of cardiovascular disease, "a lot of biomarkers don't seem to add a great deal once you take the standard risk factors into account," Wang said.

But research on those biomarkers should continue, because "there very well could be subgroups of people in which it would be useful to measure biomarkers," Wang said. "We need further data on that question."

Another reason for continuing research is that "there are studies that suggest that treating people to lower these biomarkers improves clinical outcome," he said.

But the bottom line is that "widespread use of biomarkers is not indicated at this time for clinical purposes," Wang said.

"The message in the article is that the cycle of enthusiasm and hope that we have found the holy grail has been shot down," said James H. Ware, dean for academic affairs at the Harvard School of Public Health, who wrote an accompanying commentary.

Researchers have tended to hope that a newly discovered biomarker "might be a great advance in the ability of a doctor to take individual patients and make a diagnosis," Ware said. "But a lot of these things don't have much use as diagnostic tools."

"People will be more cautious as new biomarkers emerge," he added.

But research should continue because "diseases like cardiovascular disease are very complicated, multi-factorial phenomena," Ware said. "There is not one pathway that leads to impairment of the heart, so a description of it is bound to be complicated."

One useful lesson of the study is that "our data provide a useful reminder that traditional risk factors are very important," Wang said. "They set the bar very high in terms of the knowledge they give us. It takes a fair amount to improve on what we already have."

Traditional Heart Risk Factors Outdo Biomarkers

The sophisticated biomarkers for cardiac risk that have enthralled researchers in recent years don't add much diagnostic power to such traditional risk factors as blood cholesterol levels, smoking, blood pressure and obesity, a new study finds.

"Our results indicate that, at least for clinical use, they are not ready for prime time," said study author Dr. Thomas J. Wang, an assistant professor of medicine at Harvard University and a member of Massachusetts General Hospital's cardiovascular division. The report is published in the Dec. 21 issue of the New England Journal of Medicine.

Wang and his colleagues followed 3,209 participants in the Framingham Heart Study for a decade, measuring biomarkers that included C-reactive protein, homocysteine, urinary albumin, fibrinogen and natriuretic peptides.

While those measurements did provide indicators of increased risk of cardiovascular disease, "a lot of biomarkers don't seem to add a great deal once you take the standard risk factors into account," Wang said.

But research on those biomarkers should continue, because "there very well could be subgroups of people in which it would be useful to measure biomarkers," Wang said. "We need further data on that question."

Another reason for continuing research is that "there are studies that suggest that treating people to lower these biomarkers improves clinical outcome," he said.

But the bottom line is that "widespread use of biomarkers is not indicated at this time for clinical purposes," Wang said.

"The message in the article is that the cycle of enthusiasm and hope that we have found the holy grail has been shot down," said James H. Ware, dean for academic affairs at the Harvard School of Public Health, who wrote an accompanying commentary.

Researchers have tended to hope that a newly discovered biomarker "might be a great advance in the ability of a doctor to take individual patients and make a diagnosis," Ware said. "But a lot of these things don't have much use as diagnostic tools."

"People will be more cautious as new biomarkers emerge," he added.

But research should continue because "diseases like cardiovascular disease are very complicated, multi-factorial phenomena," Ware said. "There is not one pathway that leads to impairment of the heart, so a description of it is bound to be complicated."

One useful lesson of the study is that "our data provide a useful reminder that traditional risk factors are very important," Wang said. "They set the bar very high in terms of the knowledge they give us. It takes a fair amount to improve on what we already have."