Over the past couple of decades, unregulated nonstandard oncology approaches have gained growing popularity among cancer patients. The relatively new field of integrative oncology was established to promote a more holistic and multidisciplinary approach to cancer care and to encourage scientific and evidence-based evaluation and appropriate clinical integration of complementary therapies. Nationally regarded breast cancer specialist Debu Tripathy, MD, Professor of Medicine and Clinical Leader of the Women's Cancer Research Program, University of Southern California and Norris Comprehensive Cancer Center, spoke withThe ASCO Postabout the current state of integrative oncology and the importance of further research in this area.

Important Nuance

Dr. Tripathy stressed that differentiating the terms complementary and alternative is essential. He explained that the formal definition of integrative medicine is using complementary interventions that are not considered part of mainstream Western medicine and combining them with standard therapy, whereas alternative medicine is taking nonstandard approaches and using them as the primary therapy, as an alternative to evidenced-based medicine.

"The concern is that unproven therapies that are harmful might be used instead of proven treatments. However, where evidence of benefit exists, we can integrate various complementary approaches into standard care, to improve quality of life and possibly even cancer-related outcomes. So the term integrative has more or less replaced complementary, being a more holistic definition of the approach," said Dr. Tripathy.

Accepted Integrative Modalities

Dr. Tripathy explained that there is a wide range of modalities encompassed by integrative oncology, many of which have theoretical underpinnings indicating clinical benefit. These include mind-body, meditation, acupuncture, and group therapy. "It may also extend to systems-based forms of medicine such as Chinese or Ayurvedic medicine where there is a combination of lifestyle modification or in some cases herbal or even homeopathic medicine, for which we don't have good evidence of efficacy at this time," he said.

These diverse approaches have different levels of evidence associated with them, Dr. Tripathy noted. "Some approaches have a reasonable amount of data from randomized trials, such as acupuncture, which has clearly been shown to improve pain control in certain situations when side effects from other modalities are clinically significant. In fact, many payers now reimburse for acupuncture," he said, adding that acupuncture has recently shown benefits in chemotherapy-induced nausea.

Higher Stakes

Dr. Tripathy cautioned that although some herbal and botanical medicines might have potential benefits, these compounds could produce rare but dangerous side effects or adverse herb-drug interactions for patients undergoing chemotherapy. "We need prospective randomized trials to evaluate these approaches in a similar fashion to how any other drug is tested. Our group has obtained investigational new drug (IND) licenses from the FDA to conduct early trials with certain herbs that might contain a mixture of compounds that work synergistically to confer anticancer benefits," commented Dr. Tripathy.

From Theory to Trial

"If you think about it in evolutionary terms, many plants and herbs evolved symbiotically with higher-level organisms. Beneficial health effects may have evolved over time such that many components found in an herb can make the host healthier, in some cases protecting them against infection or other disease, and this in turn allows the host to spread the seeds to propagate the plant," said Dr. Tripathy.

Many currently used drugs come from natural products. "In our experience in the laboratory, we've isolated the anticancer activity of certain herbs, but with certain botanicals, when you begin to fractionate different compounds from the herbal extract either by size or charge, you begin to lose the activity. However, when you reconstitute the fractions, you regain the activity-suggesting several active compounds working in synergy. Clearly in some cases you therefore need to test the whole herbal extract, but that makes it very difficult to obtain regulatory approval," said Dr. Tripathy.

Ongoing Trials

Dr. Tripathy's group has worked in a couple of areas. One has been looking at the antitumor effects of an herb called Ban Zhi Lian (BZL 101), which has been used for centuries in Chinese medicine for both its anti-inflammatory and purported antitumor effects. "We showed in the laboratory that the compound inhibited glycolytic pathways preferentially used by tumor cells and was selective against many different cancer cell lines, including breast and pancreatic cancer, compared with normal cells," said Dr. Tripathy.

A safety study they initiated found some gastrointestinal side effects such as bloating and gas, probably due to the insoluble herbs, so we gave them a different preparation and reduced the fiber content. "We then conducted another phase I study and actually saw some minimal responses on serial tumor scans. In fact, some patients just came short of a formal response, and we've just submitted a grant to conduct a phase II trial to assess efficacy."

They are also looking at the herb Menerba, which has a targeted mechanism of action that activates only the estrogen receptor beta pathway, and can thereby inhibit hot flashes. "Unlike estrogen-based hormone therapy, Menerba does not activate the estrogen receptor alpha pathway, known to be implicated in both breast and uterine cancer development," remarked Dr. Tripathy.

The trial-a randomized, double-blinded, placebo-controlled study that enrolled 217 healthy postmenopausal women at six clinical sites-provided evidence that treatment with Menerba reduced the frequency of hot flashes in healthy postmenopausal women and the drug was well tolerated. A larger phase III trial is underway.

Conclusions

"Integrative oncology is very young field, but we have laboratory data that show potential. We now need well-conducted studies to prove benefits, but there are two reasons funding is difficult to obtain," said Dr. Tripathy.

First, government grants are subject to peer review from scientists who come from a strictly traditional view, and they tend to be skeptical about nonstandard approaches. And second, because you cannot patent these compounds, funding from the private sector is equally difficult to obtain. Consequently, most of the research in this area has been limited to very small pilot studies, which may indicate safety but are just too small to prove efficacy.

But until we have data from more definitive trials of botanical agents, Dr. Tripathy said, "health-care professionals should be able to at least provide evidence-based, patient-centered advice to guide patients regarding the benefits of certain proven integrative approaches, while counseling to avoid those that might be harmful." ■

Disclosure: Dr. Tripathy reported no potential conflicts of interest.