Kristine M. Conner
University of Pennsylvania Cancer Center
Last Modified: October 23, 2000
Some recent scientific studies, combined with anecdotal evidence from doctors and nurses, suggest that many cancer patients are using so-called "unconventional medical therapies" while they are undergoing radiation, chemotherapy, or other conventional cancer treatments. The most commonly used unconventional therapies range from vitamins and herbal supplements to biofeedback and image therapy to other natural products like shark cartilage. Unlike conventional therapies, which are widely practiced, scientifically proven, and FDA-approved, and investigational therapies, which are currently under investigation in clinical trials, these unconventional treatments generally have not been proven in cancer clinical trials. And it is not yet known whether taking them in conjunction with conventional treatments is helpful or harmful.
A Monday afternoon panel presentation on "Unconventional Medical Therapies and the Cancer Patient" was designed to get radiation oncologists talking about this every issue. Moderated by OncoLink Associate Editor James Metz, MD, the panel focused primarily on the many unknowns involved in taking over-the-counter vitamins and herbal supplements during cancer treatment. Dr. Metz, a radiation oncologist at the University of Pennsylvania, was joined by Dr. Robert Di Paolo of the Cancer Institute of New Jersey, who has done research on a particular herbal supplement and prostate cancer, and oncology clinical nurse Jamie Meyers, RN, who has developed a special interest in natural supplements.
During his opening presentation, Dr. Metz told his standing-room-only audience that the very first unknown they face is whether or not their patients are even taking any supplements or other unconventional therapies. "If you don't ask them directly," Dr. Metz said, "they won't tell you."
That was precisely the conclusion reached by Metz and his colleagues at the University of Pennsylvania in a recent study of cancer patients' use of such therapies. The researchers added direct questions about use of vitamins and herbal supplements, guided imagery and biofeedback, shark cartilage, and other natural supplements to their standard history and physical examination. They found that while only six percent of patients revealed using any of these treatments during the standard medical history, 36 percent indicated such usage when asked the additional direct questions. The most common unconventional treatments (out of the 57 that Metz and his colleagues identified) were high-dose vitamin C and E, followed by shark cartilage, garlic, and the herbal supplements St. John's Wort and echinacea. Women and multivitamin users were the most likely to use unconventional medical therapies. The type of cancer, whether breast, lung, prostate, or some other type, made little difference in the likelihood of a patient's use of unconventional therapies.
The hidden use uncovered by this study suggests that many more cancer patients may be using such therapies than oncologists realize. It is important to ask about them directly, Metz said, because these therapies, particularly vitamin and herbal supplements, may actually impact the success of a patient's treatment. "Biochemical pathways can be affected," said Metz, "and certain drug concentrations may change and affect the toxicity of treatments. And this may hinder the effectiveness of chemotherapy and radiation therapy." Information from prospective clinical trials is needed before we can fully understand how these supplements may interact with conventional treatments. Metz also noted that there is the added complication of differentiating a placebo response on perceived symptoms from any real effect on the organic disease process.
In the meantime, he emphasized, opening up the lines of communication between physician and patient on this topic is essential. That was one of the goals in his study, which aimed to create what he called "a non-threatening environment" that would encourage patients to discuss their use of other therapies. He reminded his audience to keep in mind that patients are constantly encountering advertisements and Web sites promising better alternatives to conventional therapies. Showing examples of two advertisements that use scare tactics to promote miracle treatments, Metz told physicians that they need to be able to talk about such treatments with their patients, helping them distinguish "what's safe" from "what's a hoax." Physicians can alert their patients to look out for certain "red flags" that indicate a treatment may be a hoax, such as the claims that it has no side effects, can replace conventional therapies, and that is can cleanse the body of toxins. Since people are now spending more money out-of-pocket on alternative medicines than ever before, oncologists need to keep in mind that many of their patients are likely using unconventional therapies.
"We still need to differentiate those treatments that may offer benefits from those that harm," said Metz. "We need more information to determine which treatments safely complement conventional treatments." In the meantime, he urged physicians not to "count out" those patients who say they are using unconventional treatments and instead to "keep an open mind" about discussing them and learning more about them.
A few years ago, one of Dr. Di Paolo's prostate cancer patients exhibited an astounding drop in PSA levels after taking PC-SPES for just a month. The fifty-five-year-old male, who had a PSA level of 34 even after being treated for prostate cancer, started taking PC-SPES while waiting to enroll in a clinical trial. After just a few weeks, his PSA level had dropped to 0.4. He also experienced a drop in testosterone levels, breast enlargement, and a loss of libido.
Through subsequent lab and animal studies, Dr. Di Paolo and his colleagues determined that PC-SPES actually mimics the effect of the female hormone estrogen, counteracting the effects of male testosterone-which is known as an "androgen-ablative effect." A clinical trial found that PC-SPES suppressed testosterone levels in 6/6 patients tested by 71 percent, and it decreased PSA levels by 64 percent in 8/8 patients. "I have yet to find a patient on whom PC-SPES does not have an androgen-ablative effect," said Di Paolo. This would seem to suggest that men who have hormone-responsive prostate cancers might actually benefit from this herbal supplement.
But this is a much too easy conclusion, he added, because we don't fully understand how PC-SPES is achieving this effect. First, researchers have not determined whether the supplement as a whole or particular components, such as licorice root, are making the difference. In fact, he and his colleagues have studied licorice root and found that it does have estrogenic effects. Also, if licorice root and PC-SPES are just doing what estrogen would do, there are real questions about whether or not this is a good thing. Yes, they may lower PSA levels, said Di Paolo, but "we need to understand the mechanism of that effect."
Our understanding is complicated by the fact that PC-SPES also has been found to induce cell death and lead to temporary anti-tumor activity in prostate cancers that are not hormone-responsive (also called hormone refractory prostate cancer). This suggests that other forces are at play besides anti-hormone effects. One hypothesis is that this compound may be able to "knock out" a receptor protein called BCL-2 that keeps the cancer cells from dying. As a result, cell death is induced. "Further studies are needed to determine the importance of these mechanisms of direct cytotoxicity," Di Paolo stressed.
Whether the effect of PC-SPES is primarily estrogenic (affecting hormone levels) or cytotoxic (causing cancer cell death), it offers a clear demonstration of why it is so important for oncologists to know what their patients are taking. If a physician is using PSA levels to make treatment decisions and assess progress, and a patient is taking PC-SPES without his or her knowledge, then obviously this could be extremely problematic. The physician could be making critical judgments based on false evidence if the patient does not volunteer this information. "If you treat men with prostate cancer, as I am sure many of you do," Di Paolo stressed, "this is one of the herbal combinations that you need to know about."
Di Paolo said that many of his patients insist on taking PC-SPES, even though he cautions them that the mechanism is not fully understood and that the drop in PSA levels may be accompanied by other effects that are not yet known. In such cases, he stressed, it is important to follow patients closely and keep a dialogue going.
Myers quickly ran through a list of seven natural supplements that are among the most popular and most likely to be encountered by physicians: echinacea, essiac, garlic, ginseng, gingko biloba, green tea, and St. John's Wort. She touched on what is known about the pros and cons of each one, with the "cons" usually being side effects or the potential for interference with other medications. For example, St, John's wort is suspected of decreasing the efficacy of certain medications, Myers said, so this is "not one you would want to use in conjunction with anti-neoplastic therapies." She also reviewed any available evidence about anti-cancer effects. With garlic, she said, there is "some preliminary indication of immune system enhancement and slowing of malignant cells," and animal studies have suggested some benefit for bladder, stomach, and thyroid cancers. A recent review of 17 green tea studies by researchers at the University of Texas found that while 15 of the studies indicated an anti-cancer protective effect, two suggested the opposite conclusion that it may actually contribute to pancreatic and esophageal cancers. Clearly, then, the jury is still out on these widely available supplements, and more research is necessary.
Perhaps the most serious unknown about these supplements and other megavitamins is whether they actually might protect cancer cells against the damaging effects of chemotherapy and radiation therapy. These conventional treatments work by intentionally damaging the make-up of the cancer cell. If the supplements and megavitamins do indeed boost the immune system and/or make healthy tissue stronger, they might also give cancer cells a boost and help them ward off the damage that treatments are designed to inflict. "Does the potential for cytoprotection extend to the tumor is addition to reducing toxicities?" asked Myers. "Are they protecting healthy tissue alone, or also cancer tissue?" In other words, a patient might be taking a supplement to help the immune system fight the cancer, but in reality may be compromising the effectiveness of his or her treatment with conventional therapies.
Until this is better understood through clinical trials, she added, most experts "err on the side of being conservative" and recommend that cancer patients stop taking vitamin supplements-especially the antioxidants vitamin C and E-and other supplements before starting cancer treatment.
Other potentially beneficial treatments that do not pose this risk of treatment interference, Myers added, include massage and acupressure for nausea and vomiting. Another widely available supplement that appears to reduce cancer treatment side effects without compromising effectiveness is glutamine. Clinical trials are now looking at this very issue; for example, a trial at the Mayo Clinic is looking at whether glutamine can be used safely with Paclitaxel to reduce the joint and muscle pain associated with it. Preliminary indications from this and other clinical trials are good, and Myers cited positive anecdotal evidence from a physician colleague who already prescribes glutamine.
Like Dr. Metz, Myers urged her audience to maintain and "nonjudgmental" and "open" dialogue with patients on this issue-despite the many unknowns-and to ask about the use of complementary or alternative medicines when taking a patient's history.
Nevertheless, said moderator Jim Metz, we still need prospective studies that will give us more information about whether these compounds or certain key ingredients can safely complement conventional cancer treatments.
"Patients are the driving force behind this," said Metz. "We got interested in this because of what our patients were telling us. And we weren't taught about any of this in medical school."
"The physician-patient relationship is changing," he added. He urged physicians not to get defensive when patients come to them with print-outs of information about unconventional therapies that they retrieved from the Internet. Rather, Metz asked them to see this as a way of opening up a dialogue.
Another major concern is the amount of money cancer patients are spending on over-the-counter supplements. Some commonly used supplements, such as glutatmine, are relatively inexpensive, but others are not. One perfect example is shark cartilage, which can cost as much as 3,000 dollars for a ninety-day supply. "One thing you can tell your patients for sure is that sharks do get cancer," said Dr. Metz, referring to some of his own independent research on the topic.
Many audience members expressed a desire for more information on the topic of unconventional therapies, especially nutritional, herbal, and natural supplements. The panelists endorsed the following sources as reliable: